Blood proteins in 80 women track menopause stage and link to cognitive decline in older cohorts

Researchers used blood proteomics data from several cohorts to identify biological changes associated with menopause and their links to brain aging, according to a paper on nature.com. The midlife part of the study included 80 women aged 43–58 years, staged with STRAW+10: 30 premenopausal, 26 perimenopausal and 24 postmenopausal. For comparison, 36 age-matched men were included. Serum was analysed with NULISAseq proteomics. nature.comnature.comnature.comOpen source ↗

Protein changes in midlife

Spontaneous menopause was characterized by dysregulation in inflammatory, synaptic, metabolic and Alzheimer's disease biological processes. These signals tracked more strongly with sex hormones than with age. Proinflammatory proteins were especially upregulated in women with vasomotor symptoms. nature.comnature.comnature.comOpen source ↗

According to a summary by Earth.com, the panel covered about 120 proteins, and 16 were higher in postmenopausal than in premenopausal women. Eight are involved in inflammation, four in connections between nerve cells, two in metabolism, and two are tied to Alzheimer's disease: p-tau231 and BACE1. The work was led by Madeline Wood Alexander at Sunnybrook Research Institute in Toronto, with Rowan Saloner and Kaitlin Casaletto at the University of California, San Francisco.

A validation analysis covered age-matched pre-/peri- and postmenopausal women (n = 2,814) with plasma Olink proteomics. It replicated the observed proteomic shifts and showed broader menopause-related upregulation of inflammatory and catabolic processes, plus accelerated organ and cell aging, including brain aging. nature.comnature.comnature.comOpen source ↗

Links to cognition and dementia risk

In four independent cohorts of older women (average age 60.7–72.1 years; total n = 11,925), higher menopause proteomic scores were consistently associated with cognitive aging and dementia risk. nature.comnature.comnature.comOpen source ↗ Per the Earth.com summary, in the largest group the score was also tied to a modestly higher risk of Alzheimer's dementia.

The findings come from blood samples and health records, so they link these proteins to brain aging without showing that one causes the other. Menopause occurs at an average age of 51 years, and biomarker evidence suggests that Alzheimer's disease pathophysiology begins decades before symptoms. nature.comnature.comnature.comOpen source ↗

The authors report that the molecular signatures of menopause may inform the selection of biomarkers or therapeutic targets for brain health in midlife women. nature.comnature.comnature.comOpen source ↗