Synaptic protein CSF levels relate to memory scores in individuals without dementia.Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, The Netherlands.
Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
CITA-Alzheimer Foundation, Donostia, Gipuzkoa, Spanien.
CITA-Alzheimer Foundation, Donostia, Gipuzkoa, Spanien.
University Hospital of Lausanne, Lausanne, Switzerland.
University Hospital of Lausanne, Lausanne, Switzerland.
AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
University Hospitals Leuven, Leuven, Belgium.
Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
University of Oxford, Oxford, UK.
University of Antwerp, Antwerp, Belgium.
University of Lübeck, Lübeck, Germany.
University of Gothenburg, Gothenburg, Sweden.
Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, The Netherlands.
VU University Amsterdam, Amsterdam, the Netherlands.
University of Lübeck, Lübeck, Germany.
Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, amsterdam, the Netherlands.
Sahlgrenska University Hospital, Gothenburg, Sweden.
Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, The Netherlands.
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2024 (English)Manuscript (preprint) (Other academic)
Abstract [en]
INTRODUCTION: 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 EMIF-AD MBD and 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 groups.
DISCUSSION: 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
2024. article id rs.3.rs-4607202
Keywords [en]
Synaptic proteins, cerebrospinal fluid proteomics, early Alzheimer’s disease, memory performance
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-116785DOI: 10.21203/rs.3.rs-4607202/v1PubMedID: 39108495OAI: oai:DiVA.org:oru-116785DiVA, id: diva2:1906004
2024-10-162024-10-162024-10-17Bibliographically approved