Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease
Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET on <i>N</i> = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5; range, 1.2 to 8.1) period for Aβ and tau, respectively, ~14 years after the initiation of HT. In older women (aged >70 years), HT users exhibited faster regional tau accumulation relative to non-users, localized to the entorhinal cortex and the inferior temporal and fusiform gyri, with an indirect effect of HT on cognitive decline through regional tau accumulation. In younger women (aged <70 years), HT associations with tau accumulation were negligible. Findings are relevant for optimizing menopausal treatment guidelines.
Authors
- Heidi I.L. Jacobs (ORCID: https://orcid.org/0000-0001-7620-3822)
- Reisa Anne Sperling (ORCID: https://orcid.org/0000-0003-1535-6133)
- Aaron P. Schultz (ORCID: https://orcid.org/0000-0002-0418-0999)
- Zoe B. Rubinstein
- Mabel Seto (ORCID: https://orcid.org/0000-0001-8567-2532)
- Rachel F. Buckley (ORCID: https://orcid.org/0000-0002-5356-5537)
- Jennifer S. Rabin (ORCID: https://orcid.org/0000-0003-4754-2221)
- M. Farrell (ORCID: https://orcid.org/0000-0002-2706-3218)
- Suzanne L. Baker (ORCID: https://orcid.org/0000-0003-0209-3127)
- Danielle V. Mayblyum
- Gillian Coughlan (ORCID: https://orcid.org/0000-0003-1806-702X)
- Sung‐Tsang Hsieh (ORCID: https://orcid.org/0000-0002-3188-8482)
- Kathryn V. Papp (ORCID: https://orcid.org/0000-0003-1687-4370)
- Cristina Lois
- Julie C. Price
- Dorene M. Rentz (ORCID: https://orcid.org/0000-0002-6318-9213)
- Emma G. Thibault (ORCID: https://orcid.org/0000-0002-7873-742X)
- Rory Boyle (ORCID: https://orcid.org/0000-0003-0787-6892)
- Rebecca England Amariglio (ORCID: https://orcid.org/0009-0009-5878-8930)
- Michael J Properzi (ORCID: https://orcid.org/0000-0001-7855-2372)
- Hannah M Klinger
- Keith A. Johnson (ORCID: https://orcid.org/0000-0002-5916-6043)
- Diana L Townsend
- K. Lopez
Institutions
- Brigham and Women's Hospital (US)
- Sunnybrook Health Science Centre (CA)
- Harvard University (US)
- Lawrence Berkeley National Laboratory (US)
- The University of Melbourne (AU)
- University of Toronto (CA)
- Toronto Rehabilitation Institute (CA)
- Health Sciences Centre (CA)
- Gordon Center for Medical Imaging (US)
- Massachusetts General Hospital (US)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Sunnybrook Research Institute
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1126/sciadv.adt1288
- Citations
- 15
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 17.46