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bioRxiv · 10.64898/2026.01.30.702902

Sex-specific associations between astrocytic reactivity and cognitive decline in unimpaired elderly

Reichert Plaska, C.·Jacobs, T.·Bruno, D.·Lee, S. H.·Imbimbo, B. P.·Osorio, R.·Benedet, A. L.·Ashton, N. J.·Zetterberg, H.·Pomara, N.
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Abstract

INTRODUCTIONAstrocyte reactivity may contribute to increased Alzheimers disease (AD) risk in women. Although higher plasma glial fibrillary acidic protein (GFAP) levels have been reported in women, few studies have investigated sex-specific relationships with other plasma AD biomarkers and cognition. METHODSParticipants were enrolled in the Memory Education and Research Initiative, a longitudinal community-based cohort, and underwent evaluation including blood biomarker sampling. The Alzheimers Disease Neuroimaging Initiative (ADNI) was included as a replication cohort. RESULTSUnimpaired women exhibited higher plasma GFAP levels than men (N=584). Higher baseline GFAP was associated with worse longitudinal episodic memory, exclusively in women. In addition, both higher baseline and increasing GFAP levels over time were associated with lower longitudinal plasma A{beta}42/40 ratio. The key results were replicated in the ADNI cohort. DISCUSSIONThese findings suggest that astrocytic reactivity is more pronounced in women and may contribute to sex-specific vulnerability to AD-related pathology and cognitive decline.

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Reichert Plaska, C., Jacobs, T., Bruno, D., Lee, S. H., Imbimbo, B. P., Osorio, R., Benedet, A. L., Ashton, N. J., Zetterberg, H., Pomara, N.. 2026-02-02. Sex-specific associations between astrocytic reactivity and cognitive decline in unimpaired elderly. https://doi.org/10.64898/2026.01.30.702902

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