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Background <p>Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer’s disease (AD). The apolipoprotein E (<i>APOE</i>) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain.</p> Methods <p>We used data from the Translational Biomarkers of Alzheimer’s Disease (TRIAD) cohort (<i>n</i> = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of <i>APOE</i> ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex.</p> Results <p>Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the <i>APOE</i> ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response.</p> Conclusions <p>Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of <i>APOE</i> ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.</p>

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APOE ε4 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Lydia Trudel,
  • Joseph Therriault,
  • Arthur C. Macedo,
  • Marcel S. Woo,
  • Nesrine Rahmouni,
  • Étienne Aumont,
  • Stijn Servaes,
  • Seyyed Ali Hosseini,
  • João Pedro Ferrari-Souza,
  • Bruna Bellaver,
  • Pamela L. Ferreira,
  • Tevy Chan,
  • Yi-Ting Wang,
  • Jaime Fernandez-Arias,
  • Yansheng Zheng,
  • Brandon Hall,
  • Jenna Stevenson,
  • Robert Hopewell,
  • Chris Hung-Hsin Hsiao,
  • Maxime Montembeault,
  • Jesse Klostranec,
  • Yasser Iturria-Medina,
  • Paolo Vitali,
  • Thomas K. Karikari,
  • Andrea L. Benedet,
  • Nicholas J. Ashton,
  • Eduardo Zimmer,
  • Serge Gauthier,
  • Tharick A. Pascoal,
  • Henrik Zetterberg,
  • Kaj Blennow,
  • Pedro Rosa-Neto

摘要

Background

Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer’s disease (AD). The apolipoprotein E (APOE) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain.

Methods

We used data from the Translational Biomarkers of Alzheimer’s Disease (TRIAD) cohort (n = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex.

Results

Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response.

Conclusions

Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.