ArticleJournal of Alzheimer's disease : JAD2024
Serial Cerebrospinal Fluid Sampling Reveals Trajectories of Potential Synaptic Biomarkers in Early Stages of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Neuroplasticity and immune system are related to altered grey matter networks: a cohort study in sporadic Alzheimer's disease.Brain communications · 2026Article
- Association of qEEG TAR and TBR During Eyes-Open and Eyes-Closed with Plasma Oligomeric Amyloid-β Levels in an Aging Population.Journal of clinical medicine · 2025Article
- Cerebrospinal fluid markers link to synaptic plasticity responses and Alzheimer's disease genetic pathways.Molecular neurodegeneration · 2025Article
- Cell type-specific contributions to impaired blood-brain barrier and cerebral metabolism in presymptomatic 5XFAD mice.bioRxiv : the preprint server for biology · 2025Article
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
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7 authors.
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Abstract
Background: Synaptic dysfunction is closely associated with cognitive function in Alzheimer's disease (AD), and is present already in an early stage of the disease. Objective: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum. Methods: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A-) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4-2.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia. Results: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, β-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] -0.27[0.12] to -0.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] -0.10[0.04] to -0.15[0.05]) and SCD/MCI-A+ (St.B[SE] -0.07[0.03] to -0.12[0.03]), but not in SCD/MCI-A- (pinteraction < 0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] -1.75[0.58]), but not in the other groups (pinteraction < 0.05). Conclusions: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages.
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