TY - JOUR
T1 - Synaptic protein CSF levels relate to memory scores in individuals without dementia
AU - the Alzheimer’s Disease Neuroimaging Initiative
AU - Wesenhagen, Kirsten E.J.
AU - de Leeuw, Diederick M.
AU - Tomassen, Jori
AU - Gobom, Johan
AU - Bos, Isabelle
AU - Vos, Stephanie J.B.
AU - Martinez-Lage, Pablo
AU - Tainta, Mikel
AU - Popp, Julius
AU - Peyratout, Gwendoline
AU - Tsolaki, Magda
AU - Vandenberghe, Rik
AU - Freund-Levi, Yvonne
AU - Verhey, Frans
AU - Lovestone, Simon
AU - Streffer, Johannes
AU - Dobricic, Valerija
AU - Blennow, Kaj
AU - Scheltens, Philip
AU - Smit, August B.
AU - Bertram, Lars
AU - Teunissen, Charlotte E.
AU - Zetterberg, Henrik
AU - Tijms, Betty M.
AU - Visser, Pieter Jelle
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/86000274206
UR - https://www.mendeley.com/catalogue/e84361cf-407a-3b32-95ac-88e61971d809/
U2 - 10.1186/s13195-025-01703-z
DO - 10.1186/s13195-025-01703-z
M3 - Journal articles
C2 - 40033427
AN - SCOPUS:86000274206
SN - 1758-9193
VL - 17
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 56
ER -
