Menopause and Alzheimer’s: Scientists Find a Possible Link Hidden in The Blood

The decline in hormone levels during menopause can trigger a series of molecular changes within the body. Scientists have now found evidence suggesting that some of these changes may be linked to brain aging and a future risk of dementia.

Menopause involves more than just the end of menstrual cycles; it is accompanied by a major shift in how the body functions, primarily due to a drop in hormones produced by the ovaries. Previous studies have shown that this stage of life is associated with an increased risk of cognitive changes and neurodegenerative conditions, such as Alzheimer’s disease.

However, it remains unclear exactly what occurs within the body during menopause that might explain this connection. In this study, researchers sought clues in women’s blood by analyzing thousands of proteins circulating throughout the body.

To do this, they began with a group of 80 women aged 43 to 58. The participants were carefully categorized into three phases: pre-menopause, the menopausal transition, and post-menopause. This classification was based on standardized medical criteria that account for changes in menstrual cycles and other signs of hormonal transition.

The researchers then collected blood samples and performed proteomic analysis, a technique that allows for the simultaneous measurement of numerous proteins present in a single sample.

Proteins function as small pieces of information about what is happening within the body. By comparing the set of proteins found in women at different stages, researchers were able to identify which bodily processes were most altered during menopause.

This initial analysis revealed changes in several key systems. These included processes related to inflammation, an immune system response, as well as synapses (the communication points between neurons), metabolism (responsible for converting nutrients into energy), and processes also implicated in Alzheimer’s disease.

A particularly interesting finding was that these protein alterations appeared to be more closely linked to sex hormone levels than simply to the women’s chronological age. This is significant because two women of the same age may be at different hormonal stages.

Therefore, the results suggest that the hormonal shifts characteristic of menopause may be associated with biological changes that cannot be explained solely by natural aging.

The researchers then conducted a second, much larger analysis involving 2,814 women. This time, they employed a different proteomics method, based on a technology called Olink, to determine whether the changes observed in the first group were also present in a different population. This step is significant because scientific findings become more reliable when they can be replicated using a different group of individuals and an alternative analytical technique.

The results confirmed many of the previously observed changes and revealed further evidence of an increase in processes related to inflammation and the breakdown of molecules within cells. The researchers also identified signs consistent with accelerated aging across various organs and cell types, including those in the brain.

Finally, the scientists sought to determine whether the changes observed during menopause might be linked to health issues that emerge many years later. To investigate this, they analyzed 11,925 older women, organized into four independent groups. They developed a "molecular score" based on protein alterations associated with menopause and examined whether women with higher scores exhibited greater cognitive aging or a higher incidence of dementia.

The association appeared consistently across all four groups analyzed. This does not mean that menopause directly causes Alzheimer’s disease, nor that any single specific protein is responsible for the condition.

What the study shows is that menopause is accompanied by a set of molecular changes that may be linked to brain aging and the future risk of dementia. In the future, these changes could help researchers identify biomarkers, measurable signs within the body that indicate risk or biological alterations, as well as potential new targets for treatments aimed at protecting brain health during the aging process.

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Blood proteomics of menopause map to brain aging and dementia risk

Madeline Wood Alexander, Jennifer S. Rabin, Michelle Caunca, Allesandra Iadipaolo, Louisa Cornelis, Ria Warrier, Keenan A. Walker, Nina Miolane, Veronica Augustina Bot, Brendan Wood, Hamilton Se-Hwee Oh, Tony Wyss-Coray, Albert Pham, Julia Borger, Valentina Diaz, Emily W. Paolillo, Joel Kramer, Laura Pritschet, Caitlin Taylor, Matthew S. Panizzon, Ramiro Eduardo Rea Reyes, Marisa N. Denkinger, Nicholas J. Ashton, Sterling C. Johnson, Emily G. Jacobs, Rowan Saloner, and Kaitlin B. Casaletto

Nature Medicine (Sept 22, 2026)

DOI: 10.1038/s41591-026-04648-4

Abstract: 

Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated with menopause and its links to brain aging. In n = 80 rigorously staged (STRAW+10) pre-, peri- and postmenopausal women (aged 43–58 years) with serum NULISAseq proteomics, we show that spontaneous menopause is characterized by dysregulation in inflammatory, synaptic, metabolic and Alzheimer’s disease biologic processes, which tracked more strongly with hormones than with age. Validation analyses in age-matched pre-/peri- and postmenopausal women (n = 2,814) with plasma Olink proteomics replicated the observed proteomic shifts and revealed broader menopause-related upregulation of inflammatory and catabolic processes plus accelerated organ and cell aging, including brain aging. In four independent cohorts of older women (average age, 60.7–72.1 years; total n = 11,925), higher menopause proteomic scores associated consistently with cognitive aging and dementia risk. The molecular signatures of menopause may inform the selection of biomarkers or therapeutic targets for brain health in midlife women.