Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease
In Alzheimer's disease (AD), Aß triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aß-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the associat...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/71724 |
| Acesso em linha: | http://hdl.handle.net/10230/71724 http://dx.doi.org/10.1038/s44321-024-00190-3 |
| Access Level: | acceso abierto |
| Palavra-chave: | Alzheimer&apos s Disease Microglia Sex Differences p-tau sTREM2 |
| Resumo: | In Alzheimer's disease (AD), Aß triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aß-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 Aß 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 Aß-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 Aß to p-tau axis, where women show higher Aß-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women. |
|---|