Synaptic protein CSF levels relate to memory scores in individuals without dementiaDepartment of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, the Netherlands; Nivel, the Netherlands.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, Donostia-San Sebastian, Spain.
CITA-Alzheimer Foundation, San Sebastian, Spain.
Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Department of Neurology, Medical School, Faculty of Health Sciences, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece.
Neurology Service, University Hospitals Leuven, Louvain, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Louvain, Belgium.
Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Janssen-Cilag, Buckinghamshire, UK; University of Oxford, Oxford, UK.
AC Immune SA, LLC. Beerse, Formerly Janssen R&D, Lausanne, Switzerland; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, the Netherlands.
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany; Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Oslo, Norway.
Neurochemistry Lab, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, the Netherlands.
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK; Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, the Netherlands.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, the Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
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2025 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 17, no 1, article id 56
Article in journal (Refereed) Published
Abstract [en]
BACKGROUND: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations.
METHODS: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models.
RESULTS: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these clinical groups.
CONCLUSIONS: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease.
Place, publisher, year, edition, pages
BioMed Central (BMC), 2025. Vol. 17, no 1, article id 56
Keywords [en]
Cerebrospinal fluid proteomics, Early Alzheimer’s disease, Memory performance, Synaptic proteins
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:oru:diva-119655DOI: 10.1186/s13195-025-01703-zISI: 001436234900001PubMedID: 40033427Scopus ID: 2-s2.0-86000274206OAI: oai:DiVA.org:oru-119655DiVA, id: diva2:1942049
Funder
Swedish Research Council, 2017–00915Alzheimerfonden, AF-742881The Swedish Brain Foundation, FO2017-0243NIH (National Institutes of Health), 1R01AG068398-01Swedish Research Council, 2018–02532EU, European Research Council, 681712Familjen Erling-Perssons StiftelseStiftelsen Gamla TjänarinnorThe Swedish Brain Foundation, FO2019-0228EU, Horizon 2020, 860197Alzheimerfonden, AF-930934Stiftelsen Gamla TjänarinnorHedlund foundationGun och Bertil Stohnes StiftelseLoo och Hans Ostermans Stiftelse för medicinsk forskningThe Dementia Association - The National Association for the Rights of the DementedRegion Örebro County
Note
This work has been supported by ZonMW Memorabel grant programme #733050824 (KW, BMT and PJV) and by the Innovative Medicines Initiative Joint Undertaking under EMIF-AD MBD grant agreement #115372. KB is supported by the Swedish Research Council (#2017–00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809–2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466–236), the National Institute of Health (NIH), USA, (grant #1R01AG068398-01), and the Alzheimer’s Association 2021 Zenith Award (ZEN-21–848495). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809–2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21–831376-C, #ADSF-21–831381-C and #ADSF-21–831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694), and the UK Dementia Research Institute at UCL. JG is supported by grants from Alzheimerfonden (AF-930934) and Stiftelsen för Gamla Tjänarinnor. YVF is funded by “Hjärnfonden” (FO2018-0315) grants from the Petrus and Augusta Hedlunds Foundation, the Gun och Bertil Stohnes Foundation, the Loo and Hans Osterman Foundation, the Demensförbundet, Brain Foundation “Särfond 31 Forskning Senil demens,” Region Örebro län, “Stiftelsen for Gamla Tjänarinnor,” and Demensfonden, Stockholm Sweden.
2025-03-042025-03-042026-01-23Bibliographically approved