The call for abstracts for poster presentations is now closed and the notifications of acceptance have been sent on 8th May. We received a great number of excellent submissions. We look forward to engaging discussions and the sharing of knowledge at the symposium.<\/p>\n\n\n\n
Posters will be exhibited during 15th<\/sup>– 17th<\/sup> June at the Kuopio Music Centre (Kuopionlahdenkatu 23, 70100 Kuopio, Finland). Each author is kindly requested to be present at their posters during the poster sessions I-III, if possible. <\/p>\n\n\n\n Schedule of poster sessions:<\/strong><\/p>\n\n\n\n Monday, June 15, 2026 15.30\u201316.00<\/strong> Poster Session I<\/em><\/p>\n\n\n\n Tuesday, June 16, 2026<\/strong> 10.30\u201311.00<\/strong> Poster Session II<\/em><\/p>\n\n\n\n Wednesday, June 17, 2026<\/strong> 10.00\u201310.30 <\/strong>Poster Session III<\/em><\/p>\n\n\n\n The poster panels will be at the Music Centre on Monday 15th<\/sup> June at 10 am. The posters should be placed between 10-12 am. If you will arrive later, please inform us in advance. The posters must be removed on Wednesday 17th<\/sup> June by 16.30. <\/p>\n\n\n\n If you have any questions, please contact uef-kuopioneuro50@groups.uef.fi<\/strong>.<\/p>\n\n\n\n 1. Bridging Scales: Adapting RAPSODI for High-Precision Rat Brain MRI-Histology Co-Registration\u202f<\/strong> <\/p>\n\n\n\n Authors: Ebawak Wodajo \u00b9, Omar Narvaez \u00b9, Mirabela Rusu \u00b2, Jussi Tohka \u00b9, Alejandra Sierra \u00b9 <\/p>\n\n\n\n Author affiliations:\u202f\u00b9 A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Science, University of Eastern Finland, Kuopio, Finland.\u202f\u00b2 Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.\u202f <\/p>\n\n\n\n Rationale:<\/strong> Multimodal co-registration of MRI and histology is essential for linking macrostructural and microstructural information in brain research, but\u202fremains\u202fchallenging due to differences in image contrast, scale, and tissue deformation. We adapted the RAPSODI framework, originally developed for prostate MRI-histopathology alignment, to rat brain histology and ex vivo MRI co-registration.\u202f\u202f 2.\u202fAssociation between structural changes in brain MRI and future frailty; FINGER sub-study\u202f<\/strong> <\/p>\n\n\n\n Authors: Johanna P\u00f6yh\u00f6nen (1,2), Hanna-Maria\u202fRoitto\u202f(1,3,4), Jenni Lehtisalo (1,5), Esko Lev\u00e4lahti (1), Timo Strandberg (2,6,7), Miia Kivipelto (2,8,9,10,11),\u202fRiitta\u202fAntikainen (7,12), Hilkka Soininen (5,13), Jaakko Tuomilehto (14,15,16), Tiina Laatikainen (9),\u202fAlina Solomon (5,8,10), Ruth Stephen (5,8,17), Juha Rinne (18,19), Eric Westman (8,10,11), Tiia\u202fNgandu\u202f(1,8,9)\u202f <\/p>\n\n\n\n Author affiliations:\u202f1 Department of Public Health, Finnish Institute for Health and Welfare (THL), Helsinki, Finland; 2 Department of Medicine,\u202fClinicum, University of Helsinki, Helsinki, Finland; 3 Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland; 4 Department of Geriatrics, Wellbeing Services County of\u202fPirkanmaa, Finland; 5 Institute of Clinical Medicine\/Neurology, University of Eastern Finland, Kuopio, Finland; 6 Department of Geriatrics, Helsinki University Hospital, Helsinki, Finland; 7 Center for Life Course Health Research\/Geriatrics, University of Oulu, Oulu, Finland; 8 Division of Clinical Geriatrics, Center for Alzheimer Research, Care Sciences and Society (NVS), Karolinska\u202fInstitutet, Stockholm, Sweden; 9 Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 10 Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, United Kingdom; 11 Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden; 12 Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland; 13\u202fNeurocenter, Department of Neurology, Kuopio University Hospital, Kuopio, Finland; 14 National School of Public Health, Madrid, Spain; 15 South Ostrobothnia Central Hospital,\u202fSein\u00e4joki, Finland; 16 Department of Public Health, University of Helsinki, Helsinki, Finland; 17 FINGERs Brain Health Institute, Stockholm, Sweden; 18 Turku University Hospital, Turku, Finland; 19 Turku PET Centre, University of Turku, Turku, Finland.\u202f <\/p>\n\n\n\n Rationale: <\/strong>There are\u202festablished\u202fbrain magnetic resonance imaging (MRI) biomarkers related to dementia. However, the association between MRI findings and frailty, another major geriatric syndrome,\u202fremains\u202funclear. We aimed to investigate whether brain MRI biomarkers associate with future pre-frailty or frailty over 11 years.\u202f\u202f 3. Law Clinic: Integrating Legal and Clinical Perspectives on Legal Capacity and Rights in Dementia\u202f<\/strong> <\/p>\n\n\n\n Authors: Kaisa N\u00e4kki 1; Jenni Niinim\u00e4ki 2; Mervi Issakainen 1; Noora Suhonen 3, 4; Henna\u202fNikumaa\u202f1; Juho Kalapudas 2, 5;\u202fKaijus\u202fErvasti 1; Eino\u202fSolje\u202f2, 5; Anna M\u00e4ki-Pet\u00e4j\u00e4-Leinonen 1\u202f <\/p>\n\n\n\n Author affiliations:\u202f1 Law School, University of Eastern Finland, Joensuu; 2 Institute of Clinical Medicine \u2013 Neurology, University of Eastern Finland, Kuopio; 3\u202fNeurocenter, Neurology, Oulu University Hospital, Oulu; 4 Research Unit of Clinical Medicine, Neurology, University of Oulu; 5 Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio\u202f <\/p>\n\n\n\n Rationale:<\/strong> Progressive\u202fdementias challenge\u202fpatients\u2019 overall legal position. Cognitive and neuropsychiatric symptoms may lead to legal\u202fproblems\u202feg.\u202frelated to legal capacity, service access, family matters, and guardianship. Legal aspects\u202fremain\u202fpoorly integrated into clinical research and service systems. This project develops an interdisciplinary Law Clinic model that combines medical,\u202fneuropsychological\u202fand legal\u202fexpertise. The aim is to\u202festablish\u202fa scalable research and service platform for\u202fidentifying\u202flegal needs among people with dementia and linking them with clinical findings and traits.\u202f\u202f 4. Frontotemporal dementia patient-derived iPSC neurons show synaptic dysfunction and DNA damage\u202f<\/strong> <\/p>\n\n\n\n Authors: Nadine Huber1, Tomi Hietanen1, Sami Heikkinen2, Anastasia Shakirzyanova1,\u202fDorit\u202fHoffmann1, Hannah Rostalski1,\u202fAshutosh\u202fDhingra3, Salvador Rodriguez-Nieto3, Sari K\u00e4rkk\u00e4inen4, Marja Koskuvi5, Eila Korhonen1, P\u00e4ivi Hartikainen6, Katri Pylk\u00e4s7, Johanna Kr\u00fcger8,9,10, Tarja Malm1, Mari Takalo2, Mikko Hiltunen2, Jari Koistinaho11, Anne M. Portaankorva12, Eino Solje4,6, Annakaisa Haapasalo1\u202f <\/p>\n\n\n\n Author affiliations: 1 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 2 Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland 3 German Center for Neurodegenerative Diseases (DZNE), T\u00fcbingen, Germany 4 Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland 5 Neuroscience Center, University of Helsinki, Helsinki, Finland 6 Neuro center, Neurology, Kuopio University Hospital, Kuopio, Finland 7 Translational Medicine Research Unit, Medical Research Center Oulu and\u202fBiocenter\u202fOulu, University of Oulu, and Northern Finland Laboratory Centre\u202fNordlab, Oulu, Finland 8 Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland 9\u202fNeurocenter, Neurology, Oulu University Hospital, Oulu, Finland 10 Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland 11 Helsinki Institute of Life Science, University of Helsinki, and Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki 12 Clinical Neurosciences, University of Helsinki, Helsinki, Finland\u202f <\/p>\n\n\n\n Rationale: <\/strong>Synaptic dysfunction is suggested to play\u202fa major role\u202fin frontotemporal dementia (FTD). Some of the clinical symptoms can be associated\u202fto\u202fdisturbances in the synaptic function. Here, we aim to study the underlying molecular mechanisms leading to synaptic disturbances in induced pluripotent stem cell (iPSC) \u2013derived neurons from FTD patients carrying the C9orf72 repeat expansion (C9-HRE), the most common genetic etiology for FTD, and sporadic FTD patients in comparison to healthy controls.\u202f\u202f\u202f 5. Neuromodulation of\u202fhiPSC-Derived Neurons by Electrical Stimulation to Reduce Hyperexcitability in Frontotemporal Dementia\u202f<\/strong> <\/p>\n\n\n\n Authors: Alberto Sesena-Rubfiaro1, Nadine Huber1, Viivi Pekkala1, Rebekka Fuchs1, Anssi Pelkonen1, Mireia G\u00f3mez-Budia1, Tarja Malm1, Eino Solje2,3 and Annakaisa Haapasalo1\u202f <\/p>\n\n\n\n Author affiliations: 1. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland\u202f2. Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland\u202f3. Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland\u202f <\/p>\n\n\n\n Rationale:<\/strong> Electrical brain stimulation is explored as a potential therapeutic strategy for frontotemporal dementia (FTD). For example, repetitive transcranial magnetic stimulation (rTMS) can modulate brain activity through repeated magnetic pulses that induce long-lasting synaptic changes. However, clinical outcomes\u202fremain\u202finconsistent. We have developed an in vitro capacitive electrical stimulation platform mimicking the electric field profile of TMS in patients. This system enables controlled stimulation of human induced pluripotent stem cell (hiPSC)\u2013derived neurons on microelectrode array (MEA) chips, enabling electrical stimulation and monitoring of neuronal network activity.\u202f\u202f 6. Cellular responses to traffic-related ultrafine particles and the role of NRF2 signaling as a mitigation strategy against toxicological effects\u202f<\/strong> <\/p>\n\n\n\n Authors: Donya\u202fBehzadpour1*, Riikka Lampinen1, Laura Mussalo1, Laura Salo2, Mika Ihalainen3, Olli Sippula3, Topi R\u00f6nkk\u00f62, Pasi Jalava3, Katja M. Kanninen1\u202f <\/p>\n\n\n\n Author affiliations: 1.\u202fDepartment of Health Sciences, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 2. Department of Engineering and Natural Sciences, Physics Unit, Aerosol Physics Laboratory, Tampere University, Tampere, Finland 3. Department of Environmental and Biological Sciences, Inhalation Toxicology Laboratory, University of Eastern Finland, Kuopio, Finland\u202f <\/p>\n\n\n\n Air pollution is a global health concern with serious cellular consequences. Traffic emissions are a major source of ultrafine particles (UFPs; \u2264100 nm), which are particularly harmful because their small size allows them to penetrate biological barriers and reach the central nervous system. Cellular redox balance is tightly regulated by signaling pathways, with nuclear factor erythroid 2-related factor 2 (NRF2) playing\u202fa central role\u202fin antioxidant and anti-inflammatory responses.\u202f\u202f 7. Patient-based in vitro model of cortical iPSC-neurons for studying the effects of C9orf72 repeat expansion on synaptic dysfunction in frontotemporal dementia\u202f<\/strong> <\/p>\n\n\n\n Authors: Viivi Pekkala1, Alberto\u202fSese\u00f1a\u202fRubfiaro1,\u202fDorit\u202fHoffmann1, Tomi Hietanen1, Eino Solje2,3, Nadine Huber1, Annakaisa Haapasalo1\u202f <\/p>\n\n\n\n Author affiliations: 1 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 2 Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland 3 Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio, Finland\u202f <\/p>\n\n\n\n Rationale: <\/strong>The hexanucleotide repeat expansion of the C9orf72 gene (C9-HRE) is the most common genetic cause of frontotemporal dementia (FTD). The molecular mechanisms of FTD are still not fully understood. Thus, elucidating the underlying pathophysiology of C9-HRE-associated and non-genetic (sporadic) forms of FTD is essential to increase our understanding of disease mechanisms in\u202fthe different\u202fforms of FTD. Our\u202fprevious\u202fstudies suggest deficiencies in neuronal function, including alterations in synaptic structures and neurotransmission, in FTD patient-derived neurons.\u202f\u202f 8. Psychiatric Morbidity Before Early-Onset Dementia: Longitudinal Evidence from a Population-Based Study\u202f<\/strong> <\/p>\n\n\n\n Authors: Kasper\u202fKatisko\u202f(MD,PhD)1,2 \/\/ Mikko Aaltonen (PhD)3 \/\/ Annakaisa Haapasalo (PhD)4\/\/ P\u00e4ivi Hartikainen (MD,PhD)5\/\/ Johanna\u202fKr\u00fcger\u202f(MD,PhD)6,7,8 \/\/ Eino\u202fSolje\u202f(MD,PhD)1,5\u202f <\/p>\n\n\n\n Author affiliations: 1=Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland. 2=Department of Psychiatry, Oulu University Hospital, Oulu, Finland. 3=Law School, University of Eastern Finland, Joensuu, Finland. 4=A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. 5=Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio, Finland 6=Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland. 7=MRC, Oulu University Hospital, Oulu, Finland. 8=Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland.\u202f\u202f <\/p>\n\n\n\n Rationale:<\/strong> Psychiatric conditions\u202ffrequently\u202fintersect with neurodegenerative diseases, yet the long\u2011term psychiatric trajectories preceding early\u2011onset dementia (EOD) remain insufficiently characterized. Although associations between psychiatric disorders and dementia in general have been studied, evidence focusing specifically on EOD and its subtypes is limited. This study examined temporal patterns of psychiatric diagnoses before EOD diagnosis.\u202f\u202f 9. Frequency-dependent diffusion tensor distribution imaging in the evaluation of ischemic stroke\u202f<\/strong> <\/p>\n\n\n\n Authors: Sara Gr\u00f6hn1, Angela Naranjo2, Omar Narvaez1, Maxime Yon3, Buse Buz-Yalug1, Santos Blanco2, Daniel Topgaard4, Esther Martinez-Lara2, Ma \u00c1ngeles Peinado2, Jussi Tohka1, Alejandra Sierra1\u202f <\/p>\n\n\n\n Author affiliations:\u202f1A.I. Virtanen Institute for Molecular Sciences; University of Eastern Finland, Finland. 2Department of Experimental Biology, University of Ja\u00e9n, Spain. 3University of Rennes, LTSI, Inserm-U1099, Rennes, France. 4Department of Chemistry, Lund University, Sweden\u202f <\/p>\n\n\n\n Rationale\u202f\u202f<\/strong> 10. \u202fElectrical stimulation of human primary astrocytes and iPSC-neurons in frontotemporal dementia\u202f<\/strong> <\/p>\n\n\n\n Authors: Rebekka Fuchs1, Viivi Pekkala1, Tomi Hietanen1, Dorit Hoffmann1, Eino Solje2,3, Nadine Huber1, Alberto Sesena-Rubfiaro1, and Annakaisa Haapasalo1 <\/p>\n\n\n\n Author affiliations:\u202f1.\u202fA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 2. Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland 3. Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland\u202f <\/p>\n\n\n\n Rationale.<\/strong> Electrical stimulation (ES) has been shown to improve cognitive performance in individuals suffering from neurocognitive diseases, including frontotemporal dementia (FTD). However, the underlying physiological mechanisms\u202fremain\u202fpoorly understood and need further investigation. Thus, modeling repetitive transcranial magnetic stimulation (rTMS) in vitro could\u202fprovide\u202fnovel insights into the cellular and molecular processes involved.\u202f\u202f 11.<\/strong>\u202f\u202fAssociation between the blood-based Alzheimer\u2019s disease biomarkers and diet\u202f<\/strong> <\/p>\n\n\n\n Authors: Jenni Lehtisalo 1,2, Anna Rosenberg 2,3, Esko Lev\u00e4lahti\u202f2,\u202f Anna\u202fMatton\u202f3,4,\u202fFrancesca\u202fMangialasche\u202f3,4,5, Alina Solomon 3,6,7, Henrik Zetterberg 8, Tiia\u202fNgandu\u202f1,2, Miia Kivipelto 1,3,4,5,7\u202f\u202f <\/p>\n\n\n\n Author affiliations:\u202f1.Institute\u202fof Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland 2. Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, Finland 3. Department of Neurobiology, Care Sciences and Society, Karolinska\u202fInstitutet, Stockholm, Sweden 4. FINGERS Brain Health Institute, Stockholm, Sweden 5. Theme Inflammation and Aging, Karolinska University Hospital,\u202fSweden\u202f 6. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland 7. The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK\u202f8.Department\u202fof Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The\u202fSahlgrenska\u202fAcademy, University of Gothenburg,\u202fM\u00f6lndal, Sweden\u202f <\/p>\n\n\n\n Rationale:<\/strong> Blood-based Alzheimer\u2019s disease (AD) biomarkers are gaining interest as tools for\u202foptimising\u202fprevention strategies, but understanding their associations with preventive approaches like lifestyles in cognitively unimpaired cohorts is lacking. We\u202fanalysed\u202foverall diet quality, energy intake, and macronutrients in relation to AD biomarkers in an at-risk cohort.\u202f\u202f 12.\u202fNon-Motor Symptoms Questionnaire-Based profiles in Early-Stage Dementias: A prospective Cohort Study\u202f<\/strong> <\/p>\n\n\n\n Authors: Mika Kinnunen1, Emma Vitikka2, Johanna Kr\u00fcger2,3,4,\u202fDorit\u202fHoffmann5, Annakaisa Haapasalo5, Alberto Lle\u00f36,7, Olivia Belbin6,7, Noora-Maria Suhonen2,3,4, Barbara Borroni8,9, Anne M. Portaankorva10, Laura S\u00e4is\u00e4nen1,11, Kasper Katisko1, Eino Solje1,11\u202f <\/p>\n\n\n\n Author affiliations:\u202f\u202f1Institute of Clinical Medicine \u2013 Neurology, University of Eastern Finland, Kuopio, Finland 2Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland 3Medical Research Center, Oulu University Hospital, Oulu, Finland 4Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland 5A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 6Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu\u202fi\u202fSant Pau, Barcelona, Spain 7Centro de\u202fInvestigaci\u00f3n\u202fBiom\u00e9dica\u202fen\u202fRed\u202fen\u202fEnfermedades\u202fNeurodegenerativas\u202f(CIBERNED), Madrid, Spain 8Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy 9Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio\u202fFatebenefratelli, Brescia, Italy 10Clinical Neurosciences, University of Helsinki, Helsinki, Finland 11Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio, Finland\u202f <\/p>\n\n\n\n 13. BMAL1-Dependent Circadian Regulation of the TREM2\u2013PLC\u03b32 Signaling Pathway in Human Microglia\u202f<\/strong> <\/p>\n\n\n\n Authors: Emine Erdag1, Mette Heiskanen1, Heli Jeskanen1, Nadine Huber2,\u202fTaisia\u202fRolova3, Petra M\u00e4kinen1, Inka Kervinen1, Jessica Rosa1, Annakaisa Haapasalo2, Henna Martiskainen1, Mari Takalo1, Mikko Hiltunen1\u202f <\/p>\n\n\n\n Author affiliations:\u202f1.\u202fInstitute of Biomedicine, University of Eastern Finland, Kuopio,\u202fFinland\u202f 2. A.I. Virtanen Institute of Molecular Sciences, University of Eastern Finland, Kuopio,\u202fFinland\u202f 3.Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.\u202f <\/p>\n\n\n\n Rationale:<\/strong>\u202f\u202f 14. Generation of heterozygous\u202fTyrobp\u202fknockout BV2 microglia by CRISPR-Cas9 genome editing\u202f<\/strong> <\/p>\n\n\n\n Authors: Mette Heiskanen\u00b9, P\u00e4ivi Harju\u00b9, Roosa-Maria Willman\u00b9, Mikko Hiltunen\u00b9, Henna Martiskainen\u00b9\u202f <\/p>\n\n\n\n Author affiliation:\u202f\u00b9 Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland\u202f <\/p>\n\n\n\n Rationale\u202f\u202f<\/strong> 15. Alzheimer\u2019s Disease Plasma Biomarkers in the FINGER Multidomain Lifestyle Trial: Associations with Cognition and Intervention Response and Changes Over 2 Years\u202f<\/strong> <\/p>\n\n\n\n Authors: Anna Rosenberg (1,2), Anna Matton (2,3,4), Burak Arslan (5), Andrea L. Benedet (5), Makrina\u202fDaniilidou\u202f(2,3), Jenni Lehtisalo (1,6), Esko\u202fLev\u00e4lahti\u202f(1,6), Francesca\u202fMangialasche\u202f(2,3,7), Ilaria Pola (5), Juha Rinne (8,9), Alina Solomon (4,10), K\u00fcbra Tan (5), Henrik Zetterberg (5), Tiia Ngandu (1,2,6), Miia\u202fKivipelto\u202f(2,3,4,6,7)\u202f <\/p>\n\n\n\n Author affiliations:\u202f1) Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, Finland; 2) Department of Neurobiology, Care Sciences and Society, Karolinska\u202fInstitutet, Stockholm Sweden; 3) FINGERS Brain Health Institute, Stockholm, Sweden; 4) The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK; 5) Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The\u202fSahlgrenska\u202fAcademy, University of Gothenburg,\u202fM\u00f6lndal, Sweden; 6) Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 7) Theme Inflammation and Aging, Karolinska University Hospital, Sweden; 8) Turku PET Centre, University of Turku, Turku, Finland; 9) Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland; 10) Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland\u202f <\/p>\n\n\n\n RATIONALE:<\/strong> Plasma Alzheimer\u2019s disease biomarkers can enable early disease detection and intervention, but studies are scarce in at-risk cohorts and non-pharmacological trials. We investigated plasma biomarkers in the FINGER trial.\u202f\u202f 16. Monoallelic TYROBP deletion affects TREM2 levels and disrupts myelin phagocytosis in microglial BV2 cells\u202f<\/strong> <\/p>\n\n\n\n Authors: Linnea Luhtaniemi1, Rosa Sinisalo1, Mette Heiskanen1, P\u00e4ivi Harju1, Roosa-Maria Willman1, Annakaisa Haapasalo2, Mikko Hiltunen1 and Henna Martiskainen1\u202f <\/p>\n\n\n\n Author affiliations:\u202f1 School of Medicine, Institute of Biomedicine, University of Eastern Finland 2 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland\u202f <\/p>\n\n\n\n Activation of disease-associated microglia (DAM) requires TREM2 signaling through its adaptor protein DAP12, encoded by TYROBP. Complete loss of TYROBP causes Nasu-Hakola disease,\u202fwhereas\u202fpartial loss (monoallelity) increases Alzheimer\u2019s disease (AD) risk. However, the mechanisms by which reduced DAP12 availability disrupt TREM2 signaling and microglial function are still unclear.\u202f\u202f\u202f 17. <\/strong>Associations between chronic CNS-active medication use and paired-pulse Transcranial Magnetic Stimulation (ppTMS)<\/strong> <\/p>\n\n\n\n Authors: Meri Juslin \u00b9, Laura S\u00e4is\u00e4nen \u00b2 \u00b3, Sara M\u00e4\u00e4tt\u00e4 \u00b9 \u00b2, Matti Tyrv\u00e4inen \u2074, Jelena Hypp\u00f6nen \u00b9 \u2074, Eino Solje \u00b2 \u00b3 <\/p>\n\n\n\n Author affiliations: 1 Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland. 2 Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland. 3 Neuro Center – Neurology, Kuopio University Hospital, Kuopio, Finland. 4 Institute of Clinical Medicine, Clinical Neurophysiology, University of Eastern Finland, Kuopio, Finland. <\/p>\n\n\n\n Rationale: <\/strong>Paired-pulse Transcranial Magnetic Stimulation (ppTMS) has been proposed as a potential diagnostic tool in early-stage dementing diseases. However, use of central nervous system (CNS) active medication is often listed as an exclusion criterion in ppTMS studies. For clinical applicability of ppTMS, it\u2019s essential to understand how long-term and concurrent use of CNS-active medication influence its outcomes. Most prior pharmaco-TMS studies have been conducted in a setting, where the drug is administered to a previously unmedicated subject, with ppTMS measured relatively shortly after. 18. PREDICTFTD: Accelerating the Validation of Predictive Liquid Biomarkers for Frontotemporal Dementia Diagnosis and Subclassification<\/strong> <\/p>\n\n\n\n Authors: Abbe Ullgren1,2*, Noora-Natalia Veikkolainen1, Mervi K\u00f6n\u00f6nen3, Annakaisa Haapasalo4, Harro Seelar5, Eino Solje1,6, on behalf of the PREDICTFTD Consortium *Presenting author <\/p>\n\n\n\n Author affiliations: 1 Institution of Clinical Medicine \u2013 Neurology, University of Eastern Finland, Kuopio, Finland 2 Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Solna, Sweden 3 Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland. 4 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland 5 Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 6 Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio, Finland <\/p>\n\n\n\n Rationale<\/strong> 19. Understanding the Factors Contributing to Alzheimer\u2019s Disease Misdiagnosis<\/strong> <\/p>\n\n\n\n Authors: Ave Kivisild1, Salome Ervasti2, Per Johansson3,4, Maria Landqvist Wald\u00f63,4, Kasper Katisko1, Johanna Kr\u00fcger2,5,6, Eino Solje1,7 <\/p>\n\n\n\n Author affiliations: 1 = Institute of Clinical Medicine \u2013 Neurology, University of Eastern Finland, Kuopio, Finland 2 = Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland 3= Center of Cognitive Medicine, Sk\u00e5ne University Hospital, \u00c4ngelholm, Sweden 4= Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Lund, Sweden 5 = MRC, Oulu University Hospital, Oulu, Finland 6 = Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland 7 = Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio, Finland <\/p>\n\n\n\n Rationale<\/strong> 20. <\/strong>Mid-to-late life subjective memory impairment and edentulism may jointly identify increased dementia risk<\/strong> <\/p>\n\n\n\n Authors:<\/strong> Sam Asher1,2<\/sup>, Alina Solomon2,3,4<\/sup>, & Anna Liisa Suominen1,5,6<\/sup> <\/p>\n\n\n\n Author affiliations:<\/sup><\/strong> <\/p>\n\n\n\n 1<\/sup>Institute of Dentistry, University of Eastern Finland, Kuopio, Finland <\/p>\n\n\n\n 2<\/sup>Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden <\/p>\n\n\n\n 3<\/sup>Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland 4<\/sup>Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, United Kingdom <\/p>\n\n\n\n 5<\/sup>Department of Public Health, Finnish Institute for Health and Welfare (THL), Helsinki, Finland <\/p>\n\n\n\n 6<\/sup>Oral and Maxillofacial Teaching Unit, Primary Oral Health Care Services, Wellbeing Services County of North-Savo, Kuopio, Finland <\/p>\n\n\n\n Rationale:<\/strong> Literature links subjective memory impairment and severe tooth loss with incident dementia, however, synergistic effects of these markers on incident dementia risk has not been investigated. <\/p>\n\n\n\n Methods: <\/strong>Data on participants (N=1834) without baseline dementia, depression, or functional impairment, was retrieved from Finnish Health 2000 Survey, supplemented with dementia diagnosis until 2015 from health registers. Baseline cognitive assessment included objective assessment via neuropsychological cognitive test battery and inquiries about subjective memory: experiencing recent memory decline (no\/yes), and memory changes adversely affecting daily life (no\/yes). We defined subjective memory impairment (SMI) as experiencing both memory decline and its adverse functional impact. Analysis included Cox proportional regression, tested interaction between SMI and tooth count, accounted for relevant covariates including objective compositive cognitive score, reverse causality bias, and competing mortality. <\/p>\n\n\n\n Results<\/strong>: After accounting for relevant confounders, potential reverse causality bias, and competing risk, SMI was associated with increased dementia risk. The association was independent of baseline objective cognition and tooth count, but no SMI-tooth count interaction was observed. However, significant positive interaction between SMI and edentulism (i.e., complete tooth loss) was found (p=0.047) including among participants aged \u226555years (p=0.037). In analysis stratified by edentulism, SMI increased incident dementia risk among edentate participants (HR range=3.70-3.80), but not dentate participants (having \u22651 teeth). <\/p>\n\n\n\n Conclusions: <\/strong>Subjectively meaningful memory impairment and edentulism may in conjunction identify at-risk individuals. <\/strong>Natural tooth preservation is important for healthy cognition, and integration of oral health considerations in geriatric healthcare may facilitate early identification and risk reduction. <\/p>\n\n\n\n 21. The Cerebrospinal Fluid and Plasma Proteomics of Idiopathic Normal Pressure Hydrocephalus<\/strong> <\/p>\n\n\n\n Authors: Mikolaj Wojnicki 1,2, Anssi Lipponen 2, Sami Heikkinen 2, Tony Wyss-Coray 3, Tarja Malm 4, Mikko Hiltunen 2, Ville Leinonen 1,5 <\/p>\n\n\n\n Author affiliations: 1. Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland, 2. Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland, 3. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA, 4. A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland, 5. Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland <\/p>\n\n\n\n Rationale <\/strong> 22. AMZ1\/GNA12 and SLCO1A2 Variants Are Associated with Altered Ventricular Volume in Normal Pressure Hydrocephalus<\/strong> <\/p>\n\n\n\n Authors: Umay Atalay1, Toni Tuovinen1, Nikita Keskinen1,2, Mikolaj Wojnicki1, Alli Pesola1, Joel R\u00e4s\u00e4nen1,3, Sami Heikkinen1, Anssi Lipponen1, Ville Leinonen2,3 <\/p>\n\n\n\n Author affiliations: 1 Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland (UEF); 2 Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, UEF; 3 Kuopio University Hospital. <\/p>\n\n\n\n Normal Pressure Hydrocephalus (NPH) is a chronic neurological syndrome in older adults, characterized by gait disturbance, cognitive impairment, and urinary dysfunction. The condition is marked by abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles. Although symptoms can be alleviated by draining excess CSF to abdominal cavity via shunting, many patients will continue to experience long-term impairments highlighting the need for a better understanding of disease mechanisms. A recent GWAS of NPH in FinnGen identified eight risk loci (SLCO1A2, AMZ1\/GNA12, MLLT10, CDCA2, C16orf95, PLEKHG1, ARHGEF12, and CSNK1E; R\u00e4s\u00e4nen et al., 2024). In this study, we investigated whether lead variants at these loci are associated with characteristic neuroanatomical features of NPH. Specifically, GWAS lead variants were tested for association with ventricular and CSF volumes derived from brain MRI and cNeuro software. Associated loci were further studied by identifying variants in linkage disequilibrium with the lead variants which were subjected to functional annotation. In total, 234 common variants (GWAS , minor allele frequency > 0.05) were annotated using Ensembl Variant Effect Predictor and brain expression quantitative trait loci data, followed by secondary phenotype\u2013variant association analyses. Preliminary results suggest that variants near SLCO1A2, including rs2199687 ( ), were associated with reduced ventricular and CSF volumes, whereas rs2793354 near MLLT10 ( ) showed evidence of increased ventricular volume. Variants near AMZ1\/GNA12 and CDCA2 demonstrated more mixed effects across volumetric measures. Overall, these findings link genetic risk for NPH to disease-relevant neuroanatomical phenotypes and provide basis for future studies investigating disease mechanisms and progression. <\/p>\n\n\n\n 23. Integrating Genetics, Proteomics, and in vitro Modeling to Elucidate SLCO1A2-Mediated CSF Clearance in Idiopathic Normal Pressure Hydrocephalus<\/strong> <\/p>\n\n\n\n Authors: Alli Pesola\u00b9,\u00b2; Anssi Lipponen\u00b2; Sami Heikkinen\u00b2; Joel R\u00e4s\u00e4nen\u00b9,\u00b3; Tony Wyss-Coray\u2074; Evan Macosko\u2075; Tarja Malm\u2076; Mikko Hiltunen\u00b2; Ville Leinonen\u00b9,\u00b3 <\/p>\n\n\n\n Author affiliations: \u00b9Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; \u00b2Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; \u00b3Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland; 4Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; 5Broad Institute of MIT and Harvard, Boston, USA; 6A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland <\/p>\n\n\n\n In idiopathic normal pressure hydrocephalus (iNPH) cerebrospinal fluid (CSF) clearance is impaired leading to metabolic waste accumulating in the brain. Co-occurring iNPH and Alzheimer\u2019s disease (AD) pathologies are common, showing altered CSF levels of amyloid \u03b2-42 (A\u03b242), total Tau, and phosphorylated Tau (pTau), which suggests shared mechanisms. We identified four iNPH-associated loci with a FinnGen genome wide association study, including SLCO1A2, which showed two independent signals suggesting previously unknown haplotype structure. SLCO1A2 encodes organic anion transporting polypeptide 1A2 (OATP1A2) regulating key processes in barrier-mediated clearance. We aim to identify novel molecular mechanisms influencing OATP1A2-mediated CSF clearance with proteomics, genetics and biomarker studies, and validate the mechanisms with an in vitro blood-CSF barrier model. 24. <\/strong>Mapping cognitive function assessment in the World-Wide FINGERS Network to optimise evidence for dementia risk-reduction: the WW-FINGERS Cognitive Outcome International Working Group.<\/strong> <\/p>\n\n\n\n Authors: Laboni Akter1<\/sup>, Mariagnese Barbera1,2<\/sup>, Celeste de Jager2<\/sup>, Tiia Ngandu3,4,5<\/sup>, Francesca Mangialasche5,6,7<\/sup>, Alina Solomon1,2,5<\/sup>, Miia Kivipelto2,4,5,6,7<\/sup>, on behalf of the WW-FINGERS Network and the CO-IWG Team. <\/p>\n\n\n\n Author affiliations<\/strong>: <\/p>\n\n\n\n Rationale: <\/strong>World-Wide FINGERS (WW-FINGERS) is a global scientific initiative (73 countries as of January 2026) supporting the generation of robust evidence for dementia risk-reduction through aligned methodologies, data harmonisation, and joint analysis, in multidomain intervention trials. Within WW-FINGERS, the Cognitive Outcomes International Working Group (CO-IWG) is developing a framework for cognitive outcomes harmonisation. The aim of this study was to map the available cognitive assessments\/measures in the WW-FINGERS trials. <\/p>\n\n\n\n Methods: <\/strong>In March 2025, a survey gathering basic information on study design and detailed data on cognitive assessments was completed for all CO-IWG trials. A descriptive analysis was conducted to synthesise trials\u2019 general characteristics (e.g., status, target population), and map available cognitive tests\/measures and domains assessments. <\/p>\n\n\n\n Results: <\/strong>38 trials (N=23,999) at different stages (e.g., planning, ongoing, completed) were included across multiple countries. Most focused on cognitively healthy\/at-risk populations (84%). Cognitive assessments were mostly in-person (86%) and on paper (61%) only. Most trials (86%) assessed all FINGER cognitive domains (memory, executive function, processing speed). Additionally, executive function, processing speed, and working and episodic memory domains could be assessed in \u2265 24% of the trials using \u22653 measures. Digit-span, Trail-Making-Test, and CERAD verbal fluency were the most common tests, used in 73%, 70%, and 57% of the included trials, respectively. <\/p>\n\n\n\n Conclusions:<\/strong> Mapping of the cognitive assessments across the WW-FINGERS trials showed that joint analyses to assess the effectiveness of multidomain interventions on cognitive function is possible. More work is needed to optimise the data and variables harmonisation which will enable pooling of data. <\/p>\n\n\n\n 25. EXPLORING THE NEUROPROTECTIVE ROLE OF THE PLCG2 VARIANT IN C9ORF72 REPEAT EXPANSION-ASSOCIATED FRONTOTEMPORAL DEMENTIA<\/strong> <\/p>\n\n\n\n Authors: Vili Hakosalo1, Nadine Huber1, Eino Solje2,3, Mikko Hiltunen4, Juzoh Umemori1, Mari Takalo4, Annakaisa Haapasalo1 <\/p>\n\n\n\n Author affiliations: 1 – A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. 2 – Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland. 3 – Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland. 4 – Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland <\/p>\n\n\n\n Rationale <\/strong> 26. Structural correlates of paired<\/strong>\u2011pulse TMS in cognitive impairment<\/strong> <\/p>\n\n\n\n Authors: Miika Korhonen1,2; Laura S\u00e4is\u00e4nen1,2; Abbe Ullgren1,3; Jelena Hypp\u00f6nen4,5; Sara M\u00e4\u00e4tt\u00e44,5; Johanna Kr\u00fcger6,7,8;Annakaisa Haapasalo9; Barbara Borroni10; Ville Leinonen11,12; Mikke Niinist\u00f613;Juhana Hakum\u00e4ki13;Eino Solje1,2 <\/p>\n\n\n\n Author affiliations: 1 Institute of Clinical Medicine – Neurology, University of Eastern Finland, 70211, Kuopio, Finland; 2 Neuro Center, Neurology, Kuopio University Hospital, 70211, Kuopio, Finland; 3 Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17177, Solna, Sweden; 4 Department of Clinical Neurophysiology, Kuopio University Hospital, 70211, Kuopio, Finland; 5 Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland; 6 Research Unit of Clinical Neuroscience, Neurology, University of Oulu, 90220, Oulu, Finland; 7 Neurocenter, Neurology, Oulu University Hospital, 90220, Oulu, Finland; 8 Medical Research Center, Oulu University Hospital, 90220, Oulu, Finland ; 9 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211, Kuopio, Finland; 10 Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, 25121, Brescia, Italy: 11 Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland, 70211, Kuopio, Finland; 12 Neuro Center – Neurosurgery, Kuopio University Hospital, 70211, Kuopio, Finland; 13 Department of Clinical Radiology, Kuopio University Hospital, 70211, Kuopio, Finland <\/p>\n\n\n\n Rationale <\/strong> 27. Optically enhanced plasticity in interneuron clears amyloid beta plaques in Alzheimer\u2019s disease<\/strong> <\/p>\n\n\n\n Authors: Mariia Ivanova, Lotta Esselstr\u00f6m, Delight Degu, Lisa Rampazzo, Rashid Giniatullin, Riikka Martikainen, Heikki Tanila, Tarja Malm, Juzoh Umemori <\/p>\n\n\n\n Author affiliations: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland <\/p>\n\n\n\n Alzheimer\u2019s disease (AD) is a progressive neurodegenerative condition and increasing evidence implicates dysfunction of parvalbumin-positive interneurons (PV-INs) as key regulators for network hyperexcitability and disease progression. In parallel, deficits in activity-dependent neuronal plasticity are believed to play a central role in AD-related cognitive impairment. 28. SomaNet: Weakly Supervised Instance-Level Soma Segmentation in 3D Electron Microscopy with Partial Annotations<\/strong> <\/p>\n\n\n\n Authors: Mohammad Khateri, Morteza Ghahremani, Jussi Tohka, Alejandra Sierra <\/p>\n\n\n\n Author affiliations: Mohammad Khateri, Jussi Tohka, Alejandra Sierra are with A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Morteza Ghahremani is with Munich Center for Machine Learning, Technical University of Munich, Germany <\/p>\n\n\n\n Rationale.<\/strong> The neuronal cell body, or soma, is a central landmark for studying brain organization, classifying cell types, and reconstructing neural circuits. Three-dimensional electron microscopy (3D EM) now resolves somas at nanometer scale, but identifying and outlining each individual soma across large volumes remains a major bottleneck. Manual annotation is extremely time-consuming, and in practice only a subset of somas is typically labeled, creating a need for methods that can learn from partial annotations. 29. Multimodal electrophysiological characterization of in vitro seizure-induction paradigms in resected human brain slices<\/strong> <\/p>\n\n\n\n Authors: Vera Lezhneva1, Polina Abushik1, Mireia Gomez Budia1, Anssi Pelkonen1, Nataliia Novosolova1, Liudmila Saveleva1, Henri Eronen2, Omar Narvaez1, Mastaneh Torkamani-Azar1, Tuomas Rauramaa2,4, Arto Immonen5, Ville Leinonen2,5, Antti Huotarinen2, Kuopio Epilepsy Center Epilepsy Surgery Group3, Leena Jutila3, Jussi Tohka1, Olli Gr\u00f6hn1, Reetta K\u00e4lvi\u00e4inen2,3, Alejandra Sierra1, Tarja Malm1 <\/p>\n\n\n\n Author affiliations: 1A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland 2Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland 3Kuopio Epilepsy Center, Kuopio University Hospital, Member of ERN EpiCARE, Kuopio, Finland 4Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland 5NeuroCenter Neurosurgery, Kuopio University Hospital, Kuopio, Finland <\/p>\n\n\n\n To investigate the cellular drivers of human epileptogenesis, direct analysis of pathological network dynamics within ex vivo tissues is essential. Slices of resected human cortex serve as a vital experimental framework to evaluate intrinsic neuronal traits and disrupted circuit functions in a disease-relevant setting. The present research utilized a multimodal approach incorporating extracellular microelectrode arrays (MEA) and whole-cell patch-clamp recordings to analyze cortical samples from patients with focal, drug-resistant epilepsy (Kyyri\u00e4inen et al., 2025). 30. Intellectual Disability and Biomarkers of Alzheimer\u2019s Disease and Neurodegeneration in the Evaluation of Suspected Dementia<\/strong> <\/p>\n\n\n\n Authors: Jaana Laasanen, M.D, M.Sc, PhD, Maija Kantele, M.D., Eino Solje, Assoc. Chief Phys., Assoc. Prof., Head of the Brain Research Unit <\/p>\n\n\n\n Author affiliations: Eino Solje, Institute of Clinical Medicine \u2013 Neurology, University of Eastern Finland, Kuopio ja Neuro Center \u2013 Neurology, Kuopio University Hospital, Kuopio. Jaana Laasanen, Kuopio University Hospital (the pediatric neurology clinic) and Center of expertise for disability services (Wellbeing services county of North Savo). Maija Kantele, Center of expertise for disability services (Wellbeing services county of North Savo)<\/p>\n\n\n\n Rationale <\/strong> Selected Abstracts<\/h2>\n\n\n\n
Methods:<\/strong> The dataset included na\u00efve, sham, and moderate traumatic brain injury (moTBI) subjects from a lateral fluid percussion model. Ex vivo T1-weighted MRI was\u202facquired\u202fat 11.7T with 100\u00b5m isotropic resolution; histological sections stained for Nissl and Myelin were imaged at 0.1369\u00b5m \u00d7 0.1369\u00b5m in-plane resolution with 30\u00b5m section thickness. Preprocessing included identification of missing sections and tissue deformations, binary mask generation, and histology\u202fdownsampling\u202ffor computationally\u202ffeasible\u202fslice-to-volume reconstruction. Affine registration aligned the reconstructed Nissl histology volume to the MRI volume, with accuracy evaluated using anatomical landmark pairs across cortex, ventricles, corpus callosum, and gray-white matter boundaries.\u202f\u202f
Results:<\/strong> Qualitative assessment showed strong anatomical correspondence after co-registration. Quantitative evaluation on one sham subject using Euclidean centroid distance yielded minimum, mean, and median errors of 21.2\u00b5m, 191.7\u00b5m, and 146.2\u00b5m, with 73% of landmark pairs within a sub-voxel to low multiple-voxel error range\u202frelative\u202fto MRI resolution.\u202f\u202f
Conclusions:<\/strong> Sub-voxel accuracy\u202findicates\u202fthat affine registration effectively captures gross anatomical alignment, while remaining errors\u202flikely reflect\u202flocal deformations. These findings\u202fdemonstrate\u202fthat RAPSODI is\u202fa feasible, promising framework for preclinical neuroimaging. Future work will compare linear vs. non-linear registration and expand the framework to include more subjects, Myelin stains, and\u202fdiffusion\u202fMRI contrasts.\u202f <\/p>\n\n\n\n
Methods:<\/strong> Baseline MRI data were available for 120 participants, aged 60-77 years, in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial. Frailty status (Fried phenotype) was measured at baseline, and at 2, 7, and 11 years. Assessed MRI biomarkers included total gray matter volume, left and right hippocampal volume, Alzheimer\u2019s disease signature thickness, and periventricular and deep white matter hyperintensities (WMH) by Fazekas score. The risk of future pre-frailty\/frailty was evaluated using a mixed effect logistic regression model.\u202f\u202f
Results:<\/strong> MRI biomarkers were not associated with pre-frailty\/frailty at baseline. Greater left hippocampal volume was associated with a lower risk of future pre-frailty\/frailty at 2 (OR 0.45, 95% CI 0.21-0.97, p=0.042) and 7 years (OR 0.41, 95% CI 0.19-0.85, p=0.017).\u202fHigher\u202fperiventricular WMH score was associated with\u202fhigher\u202frisk of future pre-frailty\/frailty at 2 years (OR 2.16, 95% CI 1.01-4.62, p=0.048). All associations were independent of baseline cognition.\u202f\u202f
Conclusions: <\/strong>Smaller left hippocampal volume and higher periventricular WMH score may\u202findicate\u202frisk of future frailty, in addition to dementia, highlighting the need for prevention strategies targeting both conditions. The predictive value of MRI biomarkers was independent of cognition, supporting possible shared pathophysiological mechanisms of frailty and cognitive impairment.\u202f <\/p>\n\n\n\n
Methods:<\/strong> A pilot Law Clinic was launched in 2023 at the Brain Research Unit of the UEF. Twenty patients with dementia and their adult relatives (n=40)\u202fparticipated. Patients underwent structured neuropsychological assessments. Relatives were interviewed\u202fregarding\u202ffunctional abilities and behavioral symptoms. Both groups\u202fparticipated\u202fin legally focused interviews mapping legal issues, service\u202faccess\u202fand decision-making challenges. Clinical data, interview\u202fmaterial\u202fand health records were integrated for analysis.\u202f\u202f
Results:<\/strong> Medical\u2013legal approach is\u202ffeasible, ethically\u202frobust\u202fand meaningful for participants. The pilot revealed previously unrecognized legal needs linked to\u202fdementia related\u202fsymptoms. Participants reported increased understanding of legal issues and felt empowered. The pilot supports expanding recruitment and refining standardized assessment and interview protocols.\u202f\u202f
Conclusions:<\/strong> The Law Clinic offers a novel framework for studying and addressing legal capacity and rights in dementia. By linking clinical assessments with legal analysis, it helps\u202fidentify\u202flegal vulnerabilities and supports policy and service development and legislative discussion. The project\u202festablishes\u202fa promising platform for future research and for improving participation,\u202fautonomy\u202fand rights realization.\u202f <\/p>\n\n\n\n
Methods: <\/strong>Human iPSCs were generated from C9-HRE-carrying and non-carrying FTD patients and healthy individuals from a well-characterized Finnish FTD cohort. The iPSCs were differentiated to cortical neurons using the dual SMAD inhibition approach.\u202f\u202f
Results: <\/strong>iPSC neurons derived from C9-HRE carriers developed typical C9-HRE-associated hallmarks, including RNA foci and dipeptide repeat accumulation. All FTD neurons\u202fdemonstrated\u202fincreased TDP-43 cytosolic localization, p62\/SQSTM1 accumulation, and changes in nuclear size and morphology. In addition, the FTD neurons displayed\u202freduced\u202fnumber and altered morphology of dendritic spines together with significantly altered synaptic function. These structural and functional synaptic disturbances were accompanied by upregulation of genes related to synaptic function, including synaptic signaling and glutamatergic transmission, in FTD neurons as compared to control neurons. Pathways involved in DNA repair were significantly downregulated in FTD neurons. Only one gene was differentially expressed between the sporadic and C9-HRE-carrying FTD neurons.\u202f\u202f
Conclusions: <\/strong>Our results show that the iPSC neurons recapitulate pathological changes found in FTD patient brain and strongly support the hypothesis that synaptic dysfunction is a crucial contributor to disease pathogenesis in FTD.\u202f <\/p>\n\n\n\n
Methods:<\/strong> hiPSC-derived neurons from healthy controls, sporadic and C9orf72 hexanucleotide repeat expansion (C9-HRE)-carrying FTD patients were stimulated between two parallel carbon electrodes delivering biphasic pulses at 10 Hz. Each stimulation train lasted 5 s, followed by a 25 s interval; 20 trains were\u202fapplied\/session.\u202fStimulation was performed once daily, three times\/week, for five weeks. MEA recordings were collected weekly to assess changes in neuronal network dynamics.\u202f\u202f
Results:<\/strong> Upregulation of c-Fos\u202fdemonstrated\u202feffective activation of\u202fhiPSC-derived neurons upon stimulation. MEA recordings showed that stimulation did not adversely affect neuronal viability, as\u202findicated\u202fby sustained presence of single action potentials and burst activity. C9-HRE neurons showed higher neuronal network activity compared to sporadic or control neurons, but the activity decreased and synchronized in all neurons following stimulation.\u202f\u202f
Conclusions:<\/strong> These findings suggest that capacitive electrical stimulation can modulate neuronal network activity and mitigate the hyperexcitability in FTD neurons. Our system provides\u202fa feasible\u202fplatform to test the effects of different stimulation paradigms on patient-derived neurons.\u202f\u202f <\/p>\n\n\n\n
\u202f
Exposure to UFPs can trigger toxicity, inflammation, and oxidative stress. Although UFPs can activate NRF2 as a protective response, this defense is often insufficient. Therefore, pharmacological pre-activation of NRF2 may offer a strategy to reduce UFP-induced cellular damage. However, the relationship between air pollution and NRF2 activation is not well understood, particularly in the upper respiratory tract. Cells in the olfactory mucosa,\u202flocated\u202fin the nasal cavity, are directly exposed to airborne pollutants and represent a relevant but understudied target.\u202f\u202f
\u202f
This study investigates how UFPs from\u202fdifferent sources\u202finfluence NRF2 signaling in primary human olfactory mucosa cells using air-liquid\u202finterface\u202fand submerged culture models. NRF2 activity will be measured using transcription factor assays, while expression of target genes and proteins will be analyzed by qPCR and Western blot. To assess protective effects, cells will be pretreated with NRF2 activators such as sulforaphane, dimethyl fumarate, and curcumin prior to UFP exposure.\u202f\u202f
\u202f
Overall, the study aims to evaluate NRF2 activation as a strategy to mitigate UFP-induced cellular damage and clarify its role in cellular defense mechanisms.\u202f\u202f <\/p>\n\n\n\n
Methods:<\/strong> Induced pluripotent stem cells (iPSCs) obtained from C9-HRE-carrying and sporadic FTD patients as well as healthy control individuals are differentiated into cortical neurons using overexpression of the NGN2 gene via viral transduction. Neuronal co-cultures with human primary astrocytes are used for studying changes in the synaptic functions, including expression of synaptic genes, number of synaptic puncta, and electrophysiological properties. RNA-sequencing will be performed for\u202fidentifying\u202faltered biological pathways in FTD in comparison to healthy neurons.\u202f\u202f
Results:<\/strong> The NGN2-based neuronal differentiation protocol has been\u202fvalidated\u202fand\u202foptimized\u202ffor all used iPSC lines. C9-HRE-carrying neurons expressed typical\u202fhallmarks\u202fe.g., RNA\u202ffoci\u202fand DPR proteins. All neurons expressed pre- (Syn1, Bassoon) and post-synaptic proteins (PSD95, Homer), and the number of synapses was found to stabilize at ~35 days\u202fin culture.\u202f\u202f
Conclusions:<\/strong> Neurodegenerative disorders are an increasing concern in the aging population and need urgent therapeutic solutions. Although\u202fnumerous\u202fstudies have described synaptic dysfunction in FTD, the underlying molecular mechanisms\u202fremain\u202finsufficiently understood. Understanding disease mechanisms is essential for\u202fidentifying\u202fnovel treatment targets or biomarkers.\u202f <\/p>\n\n\n\n
Methods:<\/strong> We performed a population\u2011based longitudinal case\u2013control study covering all new EOD diagnoses from 2010 to 2021 across two Finnish regions. Clinical records from dementia outpatient clinics were systematically reviewed (N=12,490), resulting in 794 validated EOD cases, including Alzheimer\u2019s disease, frontotemporal dementia (FTD), alpha-synucleinopathies, vascular, and other EOD subtypes. For each case, 10 region-, age-, and sex\u2011matched controls without neurodegenerative diseases were selected from national registries (n=7,930). Psychiatric diagnoses (ICD\u201110 F10\u2013F98) were retrieved from the Finnish Care Register for Health Care to\u202fidentify\u202fpsychiatric morbidity within 1\u201315 years preceding the dementia diagnosis.\u202f\u202f
Results:<\/strong> Across the 1\u201315-year pre\u2011diagnostic window, 28.3% of EOD cases had at least one psychiatric diagnosis, compared with 14.1% of matched controls (RR=2.01, p<0.001). Psychiatric history was most common among individuals with FTD (35.0%, RR=2.57, p<0.001) and vascular patients (42.2%, RR=2.76, p<0.001). Distinct longitudinal patterns\u202femerged\u202facross different psychiatric and EOD diagnostic subgroups.\u202f\u202f
Conclusions:<\/strong> Psychiatric disorders appear\u202fsubstantially more\u202fcommon in individuals who later develop EOD, with differences already\u202fdetectable\u202fmore than a decade prior to dementia diagnosis. These results underscore the importance of considering psychiatric symptoms as potential early indicators or risk factors for EOD and highlight subtype\u2011specific associations.\u202f <\/p>\n\n\n\n
Early detection of microstructural tissue alterations is essential for understanding the pathogenesis of neurodegenerative diseases, such as stroke or epilepsy. While conventional MRI is central in many diagnostic workflows, it often\u202ffails to\u202fcapture subtle,\u202fsubvoxel\u202fmicrostructural changes or reliably assess tissue viability. Frequency dependent diffusion tensor distribution imaging (\u03c9DTD) leverages tensor valued diffusion\u202fencoding to\u202fprobe sub voxel microstructure.\u202f\u202f\u202f
Methods\u202f\u202f<\/strong>
We performed ex vivo\u202f\u03c9DTD\u202f(11.7 T scanner, 2D\u202fmultislice\u202fspin echo sequence; b = 700\u20138000 s\/mm\u00b2; normalized anisotropy\u202fb\u0394\u202f= \u22120.5, 0, 0.5, 1; TR =\u202f800\u202fms; TE = 30\u202fms; multiple orientations (\u03b8, \u03c6); centroid frequency\u202f\u03c9cent\/2\u03c0 = 34\u2013115 Hz; in plane voxel size 80\u00d780 \u03bcm\u00b2, 250\u202f\u03bcm\u202fslice thickness) on ischemic (transient middle cerebral artery occlusion) and sham operated rat brains 24 h after reperfusion, followed by histology. Random forest models were trained to predict quantitative histological metrics directly from\u202f\u03c9DTD.\u202f\u202f
Results\u202f\u202f<\/strong>
Leave one animal out cross validation\u202findicated\u202fthat\u202f\u03c9DTD\u202freflected changes in cellularity and cellular morphology. Permutation testing confirmed that\u202f\u03c9DTD\u202foutperformed standard DTI\u202faccros\u202fperfomance\u202fmetrics (R, Q\u00b2, MAE and MSE). Feature importance estimation showed edema, disrupted cell processes, and loss of microstructural organization as major contributors to predictions.\u202f\u202f
Conclusion\u202f\u202f<\/strong>
Our findings\u202fdemonstrate\u202fthat\u202f\u03c9DTD\u202fbased predictive modeling can detect microstructural alterations associated with ischemic stroke, outperforming standard DTI metrics. Although the present study used ischemic stroke, MRI-based predictive modeling shows promise as a generalizable, biopsy free MRI biomarker approach for quantifying tissue pathology for a variety of disorders.\u202f\u202f\u202f <\/p>\n\n\n\n
Methods.<\/strong> Human induced pluripotent stem cell (iPSC)-derived neurons from healthy control individuals and sporadic as well as C9orf72 hexanucleotide repeat expansion (C9-HRE)-carrying FTD patients were co-cultured with human primary astrocytes. The cultures were electrically stimulated starting from day-in-vitro (DIV) 11 three times weekly for 10 min (5 s stimulus on, 25 s off) with biphasic pulses at 10 Hz and a voltage of 1.28 V, 8 V or 30 V until DIV 32. To assess whether ES influences cell viability, MTT assay was performed at DIV 9 and DIV 30. Also, immunocytochemical\u202fstainings\u202f(ICC) for c-Fos and synaptic markers were assessed.\u202f\u202f
Results.<\/strong> The MTT assay\u202findicated\u202fthat the astrocytes\u2019 viability was not adversely affected by ES. c-Fos\u202fexpression was upregulated in astrocytes at 8 V and 30 V, suggesting activation in response to stimulation. ICC\u202findicated\u202fthat expression of the postsynaptic protein Homer1 decreased in neurons after ES when compared to non-stimulated neurons, suggesting alterations in synaptic density.\u202f\u202f\u202f
Conclusions.<\/strong> These results suggest that ES does not compromise cell viability but activates the neuronal co-cultures at 8 V and 30 V. Furthermore, ES may contribute to synaptic remodeling as\u202findicated\u202fby changes in postsynaptic protein expression.\u202f\u202f <\/p>\n\n\n\n
\u202f
Methods:<\/strong> Data from the FINGER study (n=1259, 60-77 yrs) included diet records (baseline n=1252, 2y=1080) and plasma biomarkers (baseline n=1225, 2y=1105). For diet we calculated quality indices (FINGER adherence and healthy Nordic diet) and macronutrient intake. Phosphorylated Tau protein (ptau; 231 and 181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were\u202fanalysed\u202fusing the Alamar Biosciences\u202fNULISAseq\u202f(CNS Disease panel 120); and ptau217 with Fujirebio Lumipulse.\u202f\u202f\u202f
\u202f
Results:<\/strong> Diet quality indices were not associated with the blood biomarkers. Cross-sectionally higher carbohydrate intake was related to higher levels of ptau217, ptau231, ptau181, and\u202fNfL\u202f(p<0.05 for each) at baseline, and higher total fat was related to lower\u202fNfL(p=0.002). Longitudinally higher\u202fcarbohydrate\u202fpredicted\u202fincrease\u202fin ptau181 (p=0.018) and GFAP (p=0.008). Also, higher baseline ptau181 predicted less improvement in FINGER index (p=0.023) and higher GFAP increase in\u202fcarbohydrate\u202f(p=0.041) but decline in energy (p=0.038).\u202f\u202f
\u202f\u202f\u202f
Conclusions: <\/strong>The most consistent finding was the cross-sectional association between higher carbohydrate intake and higher level of AD biomarkers. Longitudinal associations between diet and AD biomarkers appear\u202fmultidimensional\u202fand we cannot distinguish if already\u202fvery early\u202fdisease results in changes in diet or if diet contributes to development of AD pathology.\u202f\u202f\u202f <\/p>\n\n\n\n
Background<\/strong> Current understanding of the nature and prevalence of non-motor and autonomic symptoms across dementia subtypes\u202fremains\u202fincomplete. Although Alzheimer\u2019s Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy Bodies (DLB) are primarily defined by cognitive and motor impairments, non-motor symptoms and autonomic dysfunction are increasingly recognized across these disorders. The aim of this study was to assess non-motor symptoms,\u202freflecting\u202fautonomic dysfunction in early-stage dementia, and characterize symptom profiles across different neurodegenerative dementias.\u202f\u202f
\u202f
Methods<\/strong> A total of 64 early-stage AD, 38\u202fbvFTD, and 17 DLB patients, along with 63 cognitively healthy controls (HC) were prospectively recruited from Kuopio and Oulu University Hospitals. Non-motor symptoms were assessed using the Non-Motor Symptoms Questionnaire (NMSQ), with defined in categories of gastrointestinal, neuropsychiatric, cognitive, sleep-related, and sensory motor domains across three predefined time periods prior to the baseline evaluation.\u202f\u202f
\u202f
Results<\/strong> DLB patients showed the highest prevalence of non-motor symptoms across all assessed domains. Neither the\u202fbvFTD\u202fnor the AD group\u202fexhibited\u202fdistinct disease-specific symptom profiles. However, apathy and paranoid thoughts\u202femerged\u202fearlier in\u202fbvFTD\u202fthan in AD or DLB. Diplopia was reported by\u202f14 %\u202fof DLB patients one year prior to the diagnosis (Chi-Square, p = 0.035). Neuropsychiatric and cognitive symptoms were more common in all dementia groups compared to HC (Chi-Square, p < 0.01), although no significant differences between the dementia groups were observed.\u202f\u202f\u202f
\u202f
Conclusions<\/strong>\u202fNon-motor\u202fsymptom profiles vary across dementia subtypes already in early disease stages,\u202findicating\u202ftheir potential value as early disease-specific markers.\u202f\u202f <\/p>\n\n\n\n
Although circadian disruption is a common feature of Alzheimer\u2019s disease (AD), the role of the core clock regulator BMAL1 in linking circadian dysregulation to microglial dysfunction through TREM2\u2013PLC\u03b32 signaling is not examined in human microglial models. Moreover, APOE4, the strongest common genetic risk factor for sporadic AD, is associated with impaired microglial responses and altered TREM2 signaling,\u202fwhereas\u202fthe protective PLCG2-P522R variant enhances microglial function and reduces AD risk. Together, these observations suggest that circadian regulation may interact with the APOE\u2013TREM2\u2013PLC\u03b32 axis in AD. This study aims to\u202fdetermine\u202fwhether circadian disruption alters microglial immunometabolism through the BMAL1\u2013TREM2\u2013PLC\u03b32 pathway and whether melatonin can restore microglial homeostasis.\u202f\u202f
Methods:\u202f\u202f<\/strong>
Human iPSC-derived microglia carrying wild-type or protective PLCG2-P522R, on APOE3\/3 or APOE4\/4 backgrounds, will be used. Circadian disruption will be induced by BMAL1 silencing using RNA interference or CRISPR, followed by assessment of TREM2\u2013PLC\u03b32 expression and downstream signaling. Cells will also be treated with melatonin to evaluate restoration of circadian and microglial homeostasis. Functional outcomes will include Seahorse analysis, A\u03b2 phagocytosis, reactive oxygen species, lipid droplet accumulation, cytokine expression, and RNA sequencing with pathway enrichment.\u202f\u202f\u202f
Results:\u202f\u202f<\/strong>
We hypothesize that BMAL1 disruption impairs microglial metabolism and A\u03b2 clearance through dysregulated TREM2\u2013PLC\u03b32 signaling, with greater effects in APOE4\/4 and wild-type PLCG2 cells than in PLCG2-P522R cells. Melatonin is expected to restore metabolic homeostasis and enhance A\u03b2 clearance.\u202f\u202f
Conclusions:\u202f\u202f<\/strong>
This study will define the BMAL1\u2013TREM2\u2013PLC\u03b32 axis in AD microglia and may\u202fidentify\u202fnovel targets for chronotherapeutic intervention.\u202f\u202f <\/p>\n\n\n\n
TYROBP gene encodes DAP12, a transmembrane signaling adapter protein expressed in the brain by microglia. DAP12 mediates intracellular signaling from cell surface receptors such as TREM2, which regulate microglial activity. Homozygous loss-of-function variants in TYROBP cause Nasu-Hakola disease, a rare disease characterized by bone cysts and early dementia. Recently, we\u202fidentified\u202fheterozygous TYROBP deletion as a novel risk factor for Alzheimer\u2019s disease. To investigate the effects of partial loss of DAP12 on downstream signaling and microglial activity, we used CRISPR-Cas9 genome editing to create\u202fmouse-derived microglial cell lines with heterozygous knockout (KO) of\u202fTyrobp.\u202f\u202f
\u202f
Methods\u202f\u202f<\/strong>
RNP complex targeting the exon 3 of\u202fTyrobp\u202fwas delivered to BV2 microglial cells by lipofection. Monoclonal cultures were created by FACS, and clones carrying either heterozygous (Tyrobp+\/-) or homozygous (Tyrobp-\/-) KOs of\u202fTyrobp\u202fwere\u202fidentified\u202fby Sanger sequencing and ICE analysis. Selected lines were\u202fvalidated\u202fby Western blotting for DAP12.\u202f\u202f
\u202f
Results\u202f\u202f<\/strong>
Edits were detected in 84% (62\/74) of sequenced colonies, yielding 19\u202fcandidate\u202fTyrobp+\/- and 18 candidate\u202fTyrobp-\/- monoclonal lines. We performed Western blot screening on 19\u202fTyrobp+\/- and 12\u202fTyrobp-\/- lines.\u202fTyrobp-\/- lines did not express DAP12, while\u202fTyrobp+\/- lines exhibited DAP12 levels ranging from 2\u2013107% (median 30%)\u202frelative\u202fto control cells. Based on sequencing results, DAP12 levels, and growth rates, we selected 4\u202fTyrobp+\/- and 3\u202fTyrobp-\/-lines for further experiments.\u202f\u202f
\u202f
Conclusions\u202f\u202f<\/strong>
We generated BV2 microglial cell lines carrying heterozygous KO of\u202fTyrobp. In addition, we generated homozygous\u202fTyrobp\u202fKO lines for comparison. Cell lines were used in further experiments.\u202f <\/p>\n\n\n\n
METHODS:<\/strong> FINGER included 1260 older adults without substantial cognitive impairment, randomized to 2-year multidomain lifestyle intervention vs. general health advice. Biomarkers were analyzed in all available baseline (n=1225) and 2-year (n=1105) samples, with\u202fLumipulse\u202f(ptau217) and\u202fNULISAseq\u2122 CNS Disease Panel120 (A\u03b242, 40, ptau181, ptau231, NFL, GFAP). Cognition was assessed with Neuropsychological Test Battery.\u202f\u202f\u202f
RESULTS:<\/strong> Majority (85.4%) had normal p-tau217 (<0.22\u202fpg\/ml) at baseline (8.0% intermediate, 6.6% abnormal >0.34\u202fpg\/ml). AUCs for prediction of amyloid-PET positivity were modest (e.g., ptau217: 0.72, 95% CI 0.56\u20130.88). Higher ptau217, GFAP, and A\u03b240 were associated with poorer baseline cognition. Higher levels of all biomarkers apart from A\u03b242 predicted less cognitive improvement over 2 years. Individuals with abnormal ptau217 had increased risk of memory decline (OR 1.91, 95% CI 1.12\u20133.28, vs. normal). Biomarker levels did not\u202fmodify\u202fresponse to intervention, i.e., beneficial effects were\u202fobserved\u202fboth in those with higher and lower levels. Over 2 years, biomarkers increased cohort-wide, yet changes were subtle, with most participants\u202fremaining\u202fwithin normal ptau217 range (82.1%). Biomarker changes were similar in\u202fthe intervention\u202fand control groups.\u202f\u202f\u202f
CONCLUSIONS:<\/strong> New plasma AD biomarkers, including ptau217, associate with cognitive changes and capture subtle accumulation of neuropathology\u202falready in\u202fat-risk stages prior to onset of cognitive impairment. The FINGER lifestyle intervention can\u202fbenefit\u202fcognition also in individuals with underlying AD neuropathology.\u202f\u202f <\/p>\n\n\n\n
To address this, we used BV2 mouse microglial lines generated by CRISPR-Cas9 editing, including cells lacking\u202fTyrobp\u202f(Tyrobp-\/-) or carrying a heterozygous deletion (Tyrobp+\/-), along with untargeted controls. Membrane fractions were isolated by\u202fbiotinylation\u202fto assess surface and intracellular TREM2 and evaluate TREM2 expression by Western blot. Soluble TREM2 (sTREM2) levels were measured by ELISA. Microglial phagocytic function was quantified using\u202fIncucyte\u202flive-cell imaging and uptake of\u202fpHrodo-labelled Zymosan and myelin to distinguish substrate- and pathway-specific effects.\u202f\u202f
Both full-length TREM2 and its C-terminal fragment (TREM2-CTF) were reduced in\u202fTyrobp-\/- and\u202fTyrobp+\/- cells, with markedly diminished membrane-associated TREM2-CTF and similar reductions in cytosolic fractions. Consistent with reduced availability of functional receptor at the cell surface, sTREM2 level was decreased across DAP12-deficient genotypes. Phagocytic assays showed substrate-specific alterations: myelin uptake\u2014dependent on TREM2\u2014was significantly impaired,\u202fwhereas\u202fZymosan phagocytosis was increased, consistent with a shift toward TLR4-mediated phagocytic pathways when DAP12-dependent signaling is compromised.\u202f\u202f
Together, our findings\u202findicate\u202fthat partial or complete DAP12 loss reduces functional TREM2 at the cell surface, lowers sTREM2 production, and disrupts TREM2-dependent phagocytosis while enhancing TLR4-driven uptake. These alterations highlight impaired microglial homeostasis as a potential mechanism by which monoallelic TYROBP deletion increases AD risk.\u202f\u202f <\/p>\n\n\n\n
Methods:<\/strong> The study is based on an observational study design. We evaluated 200 subjects (17 Frontotemporal dementia, 33 Alzheimer\u2019s disease, 13 Dementia with Lewy bodies, 17 parkinsonian, 15 Mild cognitive impairment, 41 Normal pressure hydrocephalus, 64 other) and 36 unmedicated healthy controls, with TMS performed at baseline and after 1 year. Subjects continued their regular medications to reflect a real-life clinical implementation. The medications were divided into 13 groups based on their primary pharmacological mechanism of action. We measured resting motor threshold (RMT) and three measures of cortical excitability: SICI-ICF, LICI and SAI; accounting for glutamatergic, GABAergic and cholinergic functions of the brain.
Results: <\/strong>Antipsychotic use was associated with a higher RMT (independent samples t-test, p < 0.05). Memantine use could only be evaluated at baseline and was associated with weaker ICF at 7 ms (independent samples t-test, p < 0.001).
Conclusions:<\/strong> The continuous use of CNS-active drugs may influence ppTMS findings and should therefore be further investigated and considered when interpreting ppTMS results in clinical settings. <\/p>\n\n\n\n
PREDICTFTD is a Horizon Europe project aiming to transform early and accurate diagnosis of frontotemporal dementia (FTD), particularly sporadic FTD, by validating predictive liquid biomarkers and enabling AI-supported, multimodal diagnostic tools. Aside from genetic testing, FTD lacks definitive diagnostic biomarkers and is often misdiagnosed, contributing to multi-year delays to correct diagnosis and missed opportunities for timely care and trial recruitment.
Methods <\/strong>
The prospective arm of PREDICTFTD aims to build a harmonized, multicenter observational cohort with baseline and annual follow-up visits, including clinical phenotyping, neuroimaging, and biospecimen collected using standardized protocols. The data collected will be used for biomarker validation and lay the foundation for developing new diagnostic tools.
Results <\/strong>
Within the first year, PREDICTFTD has established unified study protocols, set up a new study database, conducted cross-site training, and is on the verge of starting recruitment. Recruitment targets include ~195 FTD, 120 Alzheimer\u2019s disease, 55 non-neurodegenerative controls, and 130 healthy controls.
Conclusions <\/strong>
By delivering harmonised longitudinal multimodal datasets and biosamples, PREDICTFTD provides the foundation to validate minimally invasive biomarkers and train multimodal diagnostic AI tools to aid in differential diagnostic, support molecular subtyping, and enable earlier identification of disease onset. <\/p>\n\n\n\n
Early and accurate diagnosis of Alzheimer\u2019s disease (AD) is essential in the era of disease-modifying therapies but remains challenging due to nonspecific symptoms, phenotypic heterogeneity, and diagnostic overlap in early disease stages. We investigated factors associated with AD misdiagnosis and diagnostic revision following longitudinal reassessment.
Methods <\/strong>
This retrospective case-control study included patients from three university hospitals in Sweden (\u00c4ngelholm\/Lund) and Finland (Kuopio and Oulu). Misdiagnosis cases (n = 87) comprised patients initially diagnosed with AD whose diagnoses were later revised based on longitudinal follow up, genetic testing, or neuropathology. The misdiagnosis group was compared with biomarker confirmed AD patients (n = 177), verified using cerebrospinal fluid amyloid biomarkers, amyloid PET imaging, or neuropathology.
Results<\/strong>
AD misdiagnosis was significantly less frequent among patients with complete cerebrospinal fluid biomarker profiles (OR 0.13, 95% CI 0.052\u20130.32, p < 0.001), availability of CSF biomarker assessment (OR 0.09, 95% CI 0.037\u20130.233, p < 0.001), hippocampal atrophy of Scheltens grade \u2265 2 (OR 0.44, 95% CI 0.240\u20130.812, p = 0.018), and amnestic cognitive presentation (OR 0.02, 95% CI 0.005\u20130.10, p < 0.001). Lower educational attainment was associated with an increased likelihood of misdiagnosis (OR 2.49, 95% CI 1.13\u20135.50, p = 0.024). Thirty-one percent of misdiagnosed patients showed no evidence of a progressive neurodegenerative disease. Frontotemporal dementia was the most frequent revised diagnosis (22%).
Conclusions<\/strong>
AD misdiagnosis primarily occurred in patients lacking AD-typical clinical and biomarker features, emphasizing the need for careful diagnostic confirmation and longitudinal reassessment in biologically targeted treatment settings. <\/p>\n\n\n\n
Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia characterized by impaired gait and cognition and by urinary incontinence. However, limited understanding of its molecular pathophysiology and its subtypes contributes to varied treatment outcomes. To predict disease severity and progression, individual CSF biomarkers such as amyloid-beta and tau have been used. Recently, alterations in CSF and plasma proteome have been associated with cognitive impairment, but the proteomics of iNPH remain largely unexplored. To address this, we investigated how the CSF and plasma proteome is associated with iNPH, its severity and treatment response.
Methods<\/strong>
The study cohort consists of 324 iNPH patients and 106 non-iNPH individuals treated in Kuopio. Paired plasma and lumbar CSF samples underwent SomaScan aptamer-based proteomics (>11,000 proteins quantified). Additionally, iNPH patients have brain biopsy pathology as well as cognitive and gait test results. To discover how iNPH is manifested in the human proteome, we ran linear model differential expression analyses using limma and SomaDataIO R packages on iNPH diagnosis status, severity and treatment response. The biological mechanisms underlying the associated proteins were interpreted with the help of pathway analysis and by finding tissues that each protein originates from.
Results <\/strong>
Preliminary results revealed 138 CSF and 975 plasma proteins significantly altered in iNPH vs non-iNPH group (adj.p<0.05, |log2FC|>1).
Conclusions <\/strong>
We conclude that iNPH leaves a significant mark on both CSF and plasma proteome. Further analysis should advance our understanding of iNPH physiology and help identify novel disease mechanisms. <\/p>\n\n\n\n
Whole genome sequencing data from 317 Kuopio iNPH cohort patients and 718 imputed genotypes were used to define SLCO1A2 haplotypes. We will assess SLCO1A2 haplotypes by associating them with phenotypes within the Kuopio iNPH cohort, including cortical A\u03b242 and Tau immunohistochemistry, CSF proteomics, and functional and cognitive data. We will validate the results on A\u03b242 and Tau clearance testing cellular uptake by in vitro model of blood\u2013CSF barrier.
Our preliminary findings suggest that SLCO1A2 haplotypes influence the onset age of iNPH and AD, and are associated with altered CSF Tau, Tau\/A\u03b242, and pTau\/A\u03b242 ratios.
We conclude that these results support a functional role for OATP1A2 in blood-CSF barrier-mediated clearance of neurodegeneration-related proteins. Our integrative genotype-phenotype approach enables identification of CSF clearance-related genetic mechanisms and highlights SLCO1A2 as a potential contributor to regulate CSF clearance. <\/p>\n\n\n\n\n
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Frontotemporal dementia (FTD) is the second most common cause of early\u2011onset dementia, characterized by progressive neuronal degeneration leading to synaptic dysfunction and imbalanced neuronal activity. The most common genetic cause underlying FTD is a hexanucleotide repeat expansion (HRE) in the C9orf72 gene (C9\u2011HRE), with a particularly high prevalence in Finnish patients. The complex HRE region poses major challenges for disease screening and genetic correction, slowing both diagnostics and research. Recent discoveries have highlighted a rare PLCG2 P522R variant with neuroprotective gain\u2011of\u2011function effects against Alzheimer\u2019s disease (AD) and FTD, raising the possibility that PLCG2\u2011mediated mechanisms might also counteract C9\u2011HRE\u2011associated pathologies. This idea is now tested using human induced pluripotent stem cell (hiPSC)\u2013derived neuronal models from C9-HRE-carrying FTD patients.
Methods <\/strong>
We generated hiPSC lines from three C9\u2011HRE-carrying patients. Isogenic control hiPSC lines were generated with CRISPR\/Cas9. In addition, the protective PLCG2 P522R variant was introduced into both C9-HRE-carrying and isogenic control backgrounds. RNA fluorescent in situ hybridization (FISH) was used to assess pathological RNA foci across all lines.
Results <\/strong>
To date, three isogenic C9\u2011HRE\u2011corrected lines and one PLCG2 P522R knock\u2011in line have been successfully established. FISH analysis confirmed that the C9-HRE correction abolished the pathological RNA foci in the isogenic iPSCs.
Conclusions<\/strong>
Our studies represent an important step toward understanding the molecular mechanisms underlying C9\u2011HRE\u2011related pathogenesis and offer options for testing the potential PLCG2\u2011mediated neuroprotection beyond AD in FTD neurons. Next, the iPSCs will be differentiated into cortical neurons and their functionality, viability, and structural integrity will be assessed. <\/p>\n\n\n\n
Volumetric magnetic resonance imaging (MRI) and paired-pulse transcranial magnetic stimulation (TMS) are used to differentiate neurocognitive disorders, but their interrelationship remains unclear. We investigated neuroanatomical correlates of TMS parameters reflecting cholinergic, GABA-mediated, and glutamatergic dysfunction.
Methods <\/strong>
The study included 134 patients with cognitive impairment: progressive neurocognitive diseases (n=65), mild cognitive impairment (n=20), subjective cognitive impairment (n=36), and idiopathic normal pressure hydrocephalus (n=13). All underwent paired-pulse TMS and MRI with voxel-based morphometry using the cNeuro\u00ae artificial intelligence (AI) tool. Regional brain volumes were analyzed in relation to TMS parameters in the total cohort and by diagnosis.
Results <\/strong>
In the overall cohort and in progressive dementia, short-interval intracortical inhibition (interstimulus interval, ISI = 2 ms) correlated with volumes of the pallidum, ventral diencephalon, brainstem, and cerebellum. In subjective cognitive impairment, short-latency afferent inhibition (ISI 24 ms) was associated with volumes of the ventral diencephalon, thalamus, brainstem, midbrain, and inferior frontal operculum. In normal pressure hydrocephalus, intracortical facilitation (ISI 7 ms) showed a stronger correlation with medial precentral gyrus volume than in subjective cognitive impairment. Mild cognitive impairment showed a stronger inverse association between long-interval intracortical inhibition (ISI 100 ms) and medial postcentral gyrus volume.
Conclusions <\/strong>
This study demonstrates anatomically plausible, partly diagnosis-specific associations between AI-based volumetric MRI and paired-pulse TMS markers of cholinergic, GABA-mediated, and glutamatergic dysfunction in cognitive impairment. The findings support paired-pulse TMS as a non-invasive marker of biologically relevant circuit-level dysfunction linked to structural brain changes. <\/p>\n\n\n\n
To selectively enhance plasticity within PV-INs, we developed an optogenetic strategy of cell-type-specific expression of an optically activatable TrkB receptor (optoTrkB), the receptor for brain-derived neurotrophic factor (BDNF).
Activation of optoTrkB in PV-INs in vitro reduced intrinsic excitability of PV-INs and attenuated glutamate-evoked calcium responses in surrounding pyramidal neurons, consistent with dampening of hyperactive network states. In vivo activation of optoTrkB in cortical PV-INs at an advanced stage of AD pathology led to a marked decrease in both the number and size of amyloid-beta (A\u03b2) plaques, accompanied by elevated pCREB levels, a downstream marker of BDNF\/TrkB signaling, across a broad cortical region. Notably, overall microglial abundance remain unchanged. However, a modest increase in CD68 expression was detected in IBA1-positive microglia surrounding plaque cores, suggesting focal microglial activation without widespread proliferation.
These findings indicate that selective enhancement of TrkB signaling in PV-INs restores aspects of circuit plasticity and is sufficient to reduce amyloid pathology even at late disease stages. The observed plaque reduction likely arises from neuron-driven mechanisms, possibly complemented by localized microglial responses. Overall, this work highlights PV-IN\u2013specific optoTrkB activation as a promising disease-modifying strategy. <\/p>\n\n\n\n
Methods.<\/strong> We introduce SomaNet, a deep learning framework that learns to segment every soma in a 3D EM volume using only partial annotations. SomaNet uses a teacher\u2013student training strategy: a teacher model trained on the labeled somas generates reliable predictions on the unlabeled regions, which a student model uses to progressively learn from the entire volume. To separate closely touching somas, the network learns similarity relationships between neighboring voxels, producing sharp boundaries even in densely packed tissue. A 2.5D design combines a 2D network that captures the full extent of large somas within a section with a lightweight 3D component that ensures consistency across adjacent sections.
Results.<\/strong> Evaluated on 3D EM volumes of the adult Drosophila brain, SomaNet accurately segmented individual somas in dense, morphologically diverse regions and outperformed existing methods across standard segmentation metrics.
Conclusions.<\/strong> SomaNet substantially reduces annotation effort for soma segmentation in 3D EM, enabling scalable cell-type mapping, morphological analysis, and connectomic reconstruction. The framework generalizes to other 3D EM datasets, including mammalian and human tissues such as clinical epilepsy and tumor samples. <\/p>\n\n\n\n
The efficacy of two standard in vitro induction protocols, 100 \u03bcM 4-aminopyridine (4-AP) and high K\u207a\/low Mg\u00b2\u207a, was assessed for their capacity to trigger epileptiform activity. Although these paradigms are standard in rodent models, their specific effects on the reorganized synaptic circuits and unique intrinsic properties of the human epileptogenic cortex remain poorly understood. Our results indicate markedly different network outcomes between the two models. Sustained, synchronized firing patterns resembling ictal events were consistently driven by a significant depolarizing shift in resting membrane potential under high K\u207a\/low Mg\u00b2\u207a conditions. In contrast, 4-AP application failed to induce comparable tonic depolarization, resulting instead in interictal-like discharges and sporadic burst firing without achieving sustained transitions.
This study suggests that global ionic manipulation, rather than isolated potassium-channel blockade, generates a hyper-excitable state that more accurately reflects seizure activity in human tissue. These insights refine the translational utility of classical in vitro models, aiding the selection of appropriate methodologies for future human-centered epilepsy research. <\/p>\n\n\n\n
People with intellectual disability (ID) have an elevated risk of developing dementia which often presents at a younger age and with atypical symptoms. The objective is to determine whether the altered behavior or function disability observed in an aging individual with ID is attributable to a neurodegenerative memory disorder or to other causes by using memory\/neurodegenerative-related blood biomarker analyses.
To obtain information on how memory\/neurodegenerative biomarkers function in different etiologies of ID. More information is needed specifically about the aging of people with mild ID.
Methods <\/strong>