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CSF total tau as a proxy of synaptic degeneration
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Journal Article
CSF total tau as a proxy of synaptic degeneration
2025
Overview
Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer’s disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts. We observe a stronger correlation between CSF t-tau and synaptic biomarkers than neurodegeneration biomarkers in both groups. Synaptic biomarkers explain a greater proportion of variance in CSF t-tau levels compared to neurodegeneration biomarkers. Notably, CSF t-tau levels are elevated in individuals with abnormalities only in synaptic biomarkers, but not in individuals with abnormalities only in neurodegeneration biomarkers. Our findings suggest that CSF t-tau is a closer proxy for synaptic degeneration than for axonal/neuronal degeneration.
CSF total tau (t-tau), often used as a marker of neuronal damage, is more strongly linked to synaptic degeneration. Here, the authors show that t-tau better reflects synaptic dysfunction than axonal or neuronal loss in Alzheimer’s disease.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/58
/ Aged
/ Alzheimer Disease - cerebrospinal fluid
/ Alzheimer Disease - pathology
/ Atrophy
/ Biomarkers - cerebrospinal fluid
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Nerve Degeneration - cerebrospinal fluid
/ Nerve Degeneration - pathology
/ Neurofilament Proteins - cerebrospinal fluid
/ Neurogranin - cerebrospinal fluid
/ Proteins
/ Science
/ Synapses
/ Synaptosomal-Associated Protein 25
/ Synaptosomal-Associated Protein 25 - cerebrospinal fluid
