Sex differences in astrocytic reactivity and its association with cognitive decline in cognitively unimpaired older adults

Plasma GFAP is consistently higher in females than males in two longitudinal cohorts (MERI N=584; ADNI), linking astrocytic reactivity to early AD biology.

• Why it matters: Sex-specific differences in astrocytic reactivity and its cognitive relevance are unclear, limiting understanding of whether women face different early AD-related processes.
• What they did: In MERI and ADNI, baseline plasma GFAP was measured and related to plasma AD biomarkers (Aβ42/40, p-Tau231, p-Tau217, NfL) and longitudinal cognition, including tests for GFAP×sex×time interactions.
• The result: Higher baseline GFAP was associated with more AD-related biomarker profiles and steeper cognitive decline in both cohorts, while sex did not consistently modify these longitudinal associations.

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