In a recent paper published in Nature Medicine, Madeline Wood Alexander, Jennifer S. Rabin and colleagues investigated how biological changes associated with menopause may be linked to brain ageing and dementia risk. Women account for nearly two-thirds of people living with Alzheimer’s disease, yet the biological mechanisms underlying this increased risk remain poorly understood. Menopause, characterised by substantial declines in ovarian hormones such as oestrogen and progesterone, is increasingly being studied as a potential contributor to differences in brain ageing and dementia risk among women.
To explore this question, the researchers analysed blood proteomic data from almost 15,000 women across multiple international cohorts. Using advanced protein profiling techniques, they identified a set of blood proteins associated with menopausal status and developed a “menopause proteomic score”. They then examined whether this molecular signature was related to markers of brain ageing, cognitive performance and dementia risk in independent populations.
The findings suggest that menopause is associated with differences in proteins involved in inflammation, metabolism, neuronal function and Alzheimer's disease biology. Sixteen proteins were significantly elevated in postmenopausal women compared with premenopausal women, including inflammatory markers, synaptic proteins and Alzheimer’s disease-related proteins such as BACE1 and phosphorylated tau (p-tau231). Higher menopause proteomic scores were associated with less favourable cognitive performance and with biological signatures consistent with older brain age. Furthermore, the proteomic signature overlapped with biological pathways that have previously been implicated in dementia and Alzheimer's disease risk.
Importantly, the authors note that the findings do not demonstrate that menopause causes dementia. Instead, they suggest that menopause is accompanied by measurable molecular changes that may help explain why some women experience differences in cognitive ageing trajectories. The identified blood-based protein profile could provide new insights into the biological links between reproductive ageing and late-life brain health.
In conclusion, the findings suggest that menopause is associated with a distinct blood proteomic signature that may help shed light on biological pathways linked to brain ageing and dementia risk. The authors highlight the need for longitudinal studies to determine whether these molecular changes could help identify individuals at increased risk of cognitive decline and whether interventions targeting menopause-related biological processes could support healthier brain ageing in women.
Find the full article here: https://www.nature.com/articles/s41591-026-04648-4
