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 and Tharick A. Pascoal ()
Additional contact information
Carolina Soares: University of Pittsburgh
Bruna Bellaver: University of Pittsburgh
Pamela C. L. Ferreira: University of Pittsburgh
Guilherme Povala: University of Pittsburgh
Cristiano Schaffer Aguzzoli: University of Pittsburgh
João Pedro Ferrari-Souza: University of Pittsburgh
Hussein Zalzale: University of Pittsburgh
Firoza Z. Lussier: University of Pittsburgh
Francieli Rohden: University of Pittsburgh
Sarah Abbas: University of Pittsburgh
Guilherme Bauer-Negrini: University of Pittsburgh
Douglas Teixeira Leffa: University of Pittsburgh
Andréa Lessa Benedet: University of Gothenburg
Rebecca Langhough: University of Wisconsin
Tobey J. Betthauser: University of Wisconsin
Bradley T. Christian: University of Wisconsin
Rachael E. Wilson: University of Wisconsin
Dana L. Tudorascu: University of Pittsburgh
Pedro Rosa-Neto: Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Ouest-de-l’Île-de-Montréal
Thomas K. Karikari: University of Pittsburgh
Henrik Zetterberg: University of Gothenburg
Kaj Blennow: University of Gothenburg
Eduardo R. Zimmer: Universidade Federal do Rio Grande do Sul
Sterling C. Johnson: University of Wisconsin
Tharick A. Pascoal: University of Pittsburgh

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63545-5

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DOI: 10.1038/s41467-025-63545-5

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