- February 11, 2026
- Kaitlin B. Casaletto, et al., University of California San Francisco
Topic/Product:
CNS Disease Panel 120
Disease Area:
Aging, Menopause
Sample Type:
Plasma, Serum
Abstract
Menopause is a hallmark process in biological aging that has been associated with later life neurodegenerative risk. We leveraged proteomics data from multiple cohorts (N>3,000) to identify biological changes underlying menopause and its links to brain aging. In N=80 rigorously-phenotyped pre-, peri-, and postmenopausal women with serum NULISAseq proteomics, spontaneous menopause was characterized by dysregulation in inflammatory, synaptic, metabolic, and Alzheimer’s disease (AD) biologic processes, which tracked with hormones and not age. Pro-inflammatory protein upregulation was especially pronounced in women with vasomotor symptoms. In two cohorts of older women (N=94; N=100), menopause-related proteomic elevations associated with poorer cognitive outcomes and plasma AD biomarkers. Finally, validation analyses in age-matched pre- and postmenopausal women with plasma Olink proteomics (N=2,814) replicated the observed proteomic shifts and revealed menopause-related upregulation of additional inflammatory and catabolic processes. The molecular signatures of menopause may inform biomarkers or therapeutic targets for brain health in women.
Authors & Affiliations
Madeline Wood Alexander¹²³, Jennifer S. Rabin¹²³⁴, Michelle Caunca⁵, Allesandra Iadipaolo⁶⁷⁸, Louisa Cornelis⁹, Nina Miolane⁷⁹, Albert Pham¹⁰, Julia Borger¹⁰, Valentina Diaz¹⁰, Emily W. Paolillo¹⁰, Joel Kramer¹⁰, Laura Pritschet⁷¹¹, Caitlin Taylor⁶⁷, Matthew S. Panizzon¹², Ramiro Eduardo Rea Reyes¹³, Marisa N. Denkinger¹⁴, Nicholas J. Ashton¹⁴¹⁵, Sterling C. Johnson¹³¹⁶, Emily G. Jacobs⁶⁷⁸, Rowan Saloner¹⁰, and Kaitlin B. Casaletto¹⁰⁷
¹ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada
² Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
³ Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
⁴ Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
⁵ Neurovascular Division, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
⁶ Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, USA
⁷ Ann S. Bowers Women’s Brain Health Initiative, University of California, Santa Barbara, CA, USA
⁸ Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
⁹ Department of Physics, University of California, Santa Barbara, CA, USA
¹⁰ Edward and Pearl Fein Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
¹¹ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
¹² Center for Behavior Genetics of Aging, School of Medicine, University of California, San Diego, La Jolla, CA, USA
¹³ Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
¹⁴ Banner Sun Health Research Institute, Sun City, AZ, USA
¹⁵ Banner Alzheimer’s Institute, Phoenix, AZ, USA
¹⁶ Wisconsin Alzheimer’s Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA