CSF total tau as a proxy of synaptic degeneration
- Carolina Soares
- Bruna Bellaver
- Pamela C. L. Ferreira
- Guilherme Povala
- Cristiano Schaffer Aguzzoli
- João Pedro Ferrari-Souza
- Hussein Zalzale
- Firoza Z. Lussier
- Francieli Rohden
- Sarah Abbas
- Guilherme Bauer-Negrini
- Douglas Teixeira Leffa
- Andréa Lessa Benedet
- Rebecca Langhough
- Tobey J. Betthauser
- Bradley T. Christian
- Rachael E. Wilson
- Dana L. Tudorascu
- Pedro Rosa-Neto
- Thomas K. Karikari
- Henrik Zetterberg
- Kaj Blennow
- Eduardo R. Zimmer
- Sterling C. Johnson
- Tharick A. Pascoal
2025-08-29
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.