Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease

• DOI: 10.1126/sciadv.adt1288
• Publication Date: 2025-03-05T18:58:51Z
• Authors: Gillian T. Coughlan; Zoe Rubinstein; Hannah Klinger; Kelly A. Lopez; Stephaine Hsieh; Rory Boyle; Mabel Seto; Diana Townsend; Danielle Mayblyum; Emma Thibault; Heidi I. L. Jacobs; Michelle Farrell; Jennifer S. Rabin; Kate Papp; Rebecca Amariglio; Suzanne Baker; Cristina Lois; Dorene Rentz; Julie Price; Aaron Schultz; Michael Properzi; Keith Johnson; Reisa Sperling; Rachel F. Buckley
• Keywords: Hormone Therapy

Elucidating the downstream impact of exogenous hormones on aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET N = 146 baseline clinically normal women, aged 51 89 years. Women were scanned a 4.5-year (SD, 2.1; range, 1.3 10.4) 3.5-year 1.5; 1.2 8.1) period Aβ tau, respectively, ~14 years after initiation HT. In older (aged >70 years), HT users exhibited faster regional relative non-users, localized entorhinal cortex inferior temporal fusiform gyri, an indirect effect cognitive decline through accumulation. younger <70 associations negligible. Findings are relevant optimizing treatment guidelines.