# Blood-based proteomic signatures of spontaneous menopause: Implications for later-life brain aging and Alzheimer’s disease risk

## TL;DR

This study finds that menopause is linked to changes in blood proteins related to brain aging and Alzheimer's disease risk.

## Contribution

The study identifies proteomic signatures of spontaneous menopause and their associations with brain aging and Alzheimer’s disease.

## Key findings

- Proteomic changes during menopause include inflammation, synaptic, metabolic, and AD-related processes.
- Pro-inflammatory proteins are elevated in women with vasomotor symptoms.
- Menopause-related proteomic shifts correlate with worse cognitive outcomes and AD biomarkers.

## 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 hormone signaling processes. The molecular signatures of menopause may inform biomarkers or therapeutic targets for brain health in women.