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<p>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.</p>

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CSF total tau as a proxy of synaptic degeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月29日

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  • 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

摘要

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.