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<p>In Alzheimer’s disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau<sub>181</sub> determined in the cerebrospinal fluid (CSF). To assess potentially modulating effects of female sex, younger age, and ApoE4, we included 322 ADNI participants with cross-sectional/longitudinal p-tau<sub>181</sub>. To determine effects of microglial activation on p-tau<sub>181</sub>, we included 454 subjects with cross-sectional CSF sTREM2. Running ANCOVAs for nominal and linear regressions for metric variables, we found that women had higher Aβ-related p-tau<sub>181</sub> levels. Higher sTREM2 was associated with elevated p-tau<sub>181</sub>, with stronger associations in women. Similarly, ApoE4 was related to higher p-tau<sub>181</sub> levels and faster p-tau<sub>181</sub> increases, with stronger effects in female ApoE4 carriers. Our results show that sex alone modulates the Aβ to p-tau axis, where women show higher Aβ-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women.</p>

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Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月10日

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  • Davina Biel,
  • Marc Suárez-Calvet,
  • Anna Dewenter,
  • Anna Steward,
  • Sebastian N Roemer,
  • Amir Dehsarvi,
  • Zeyu Zhu,
  • Julia Pescoller,
  • Lukas Frontzkowski,
  • Annika Kreuzer,
  • Christian Haass,
  • Michael Schöll,
  • Matthias Brendel,
  • Nicolai Franzmeier

摘要

In Alzheimer’s disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau181 determined in the cerebrospinal fluid (CSF). To assess potentially modulating effects of female sex, younger age, and ApoE4, we included 322 ADNI participants with cross-sectional/longitudinal p-tau181. To determine effects of microglial activation on p-tau181, we included 454 subjects with cross-sectional CSF sTREM2. Running ANCOVAs for nominal and linear regressions for metric variables, we found that women had higher Aβ-related p-tau181 levels. Higher sTREM2 was associated with elevated p-tau181, with stronger associations in women. Similarly, ApoE4 was related to higher p-tau181 levels and faster p-tau181 increases, with stronger effects in female ApoE4 carriers. Our results show that sex alone modulates the Aβ to p-tau axis, where women show higher Aβ-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women.