Grant: Travel Awards - Institute Community Support

Menopause is a critical inflection point that sharply increases women's risk for Alzheimer's disease and may contribute to this sex difference. Yet the biological pathways linking menopause to brain aging remain unclear. Here, we used a proteomics approach - whereby many proteins are simultaneously measured in the blood - to identify biological changes across the menopause transition and explore their relevance to later life risk for Alzheimer's disease. We studied 81 women across various stages of the spontaneous menopause transition and 26 age matched men for comparison. Plasma was analyzed for sex hormones and 120 proteins related to brain health using a novel, ultrasensitive immunoassay. We identified 19 proteins that were elevated in postmenopausal women vs. premenopausal menopausal, which generally reflected changes in immune, vascular, metabolic, and synaptic biology. Notably, these biological changes tracked with hormone levels and menopause symptoms, but not with chronological age. We next investigated whether the identified menopause proteins related to later-life Alzheimer's disease outcomes in a separate cohort of older women. We found that multiple inflammatory, metabolic and synaptic proteins predicted Alzheimer's disease pathology and worse memory outcomes. Our findings suggest that menopause-related biological changes may represent potential targets for interventions to prevent or reduce the risk of Alzheimer's disease in women.