Blood-based proteomic signatures of spontaneous menopause: Implication for later-life brain aging and Alzheimer's disease risk

Wood Alexander, M., Rabin, J. S., Caunca, M., Iadipaolo, A., Cornelis, L., Miolane, N., Pham, A., Borger, J., Diaz, V., Paolillo, E. W., Kramer, J., Pritschet, L., Taylor, C., Panizzon, M. S., Rea Reyes, R. E., Denkinger, M. N., Ashton, N. J., Johnson, S. C., Jacobs, E. G., Saloner, R., Casaletto, K. B.

UCSF · medrxiv

Paper

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 (over 3,000 women) 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.

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Research summary

The paper claims that blood-based proteomic signatures associated with spontaneous menopause can inform biomarkers or therapeutic targets for brain health in women. This research is relevant as it explores biological changes linked to menopause that may contribute to neurodegenerative risks, addressing underlying mechanisms of aging rather than merely treating symptoms.

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