TY - JOUR
T1 - Synaptic protein CSF levels relate to memory scores in individuals without dementia
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
AU - Alzheimer's Disease Neuroimaging Initiative (ADNI)
PY - 2025/3/3
Y1 - 2025/3/3
N2 - BackgroundWe 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.MethodsWe 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.ResultsSubsets 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.ConclusionsSynaptic 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 - BackgroundWe 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.MethodsWe 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.ResultsSubsets 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.ConclusionsSynaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease.
KW - Synaptic proteins
KW - Cerebrospinal fluid proteomics
KW - Memory performance
KW - Early Alzheimer's disease
KW - MILD COGNITIVE IMPAIRMENT
KW - ALZHEIMERS-DISEASE
KW - AMYLOID-BETA
KW - NEUROGRANIN
KW - PROGRESSION
KW - DECLINE
KW - TAU
KW - ASSOCIATION
KW - ASTROCYTES
KW - OLIGOMERS
U2 - 10.1186/s13195-025-01703-z
DO - 10.1186/s13195-025-01703-z
M3 - Article
SN - 1758-9193
VL - 17
JO - Alzheimer's Research & Therapy
JF - Alzheimer's Research & Therapy
IS - 1
M1 - 56
ER -