Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline

Does female sex and aggregated amyloid-β (Aβ) synergistically influence plasma phosphorylated tau 217 (p-tau217) level, and does level of p-tau217 predict sex-specific regional tau aggregation (as measured with positron emission tomographic neuroimaging)?Women showed elevated plasma p-tau217 levels at higher aggregated Aβ compared with men, and for a given level of p-tau217, women showed greater cross-sectional and longitudinal tau accumulation relative to men across multiple brain regions. A secondary analysis also suggested that women tend to show faster cognitive decline than men when p-tau levels are high.Sex differences in tau pathology and cognitive decline may stem from Aβ-related p-tau, suggesting the need to consider sex in Alzheimer disease mechanisms and potential interventions targeting p-tau.

Corresponding Authors: Gillian T. Coughlan, PhD, MSc (gcoughlan@mgh.harvard.edu) and Rachel F. Buckley, PhD (rfbuckley@mgh.harvard.edu), Department of Neurology, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129.

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