---
title: "Blood proteomics of menopause reveal links to brain aging and dementia risk"
id: "nature-2-blood-proteomics-of-menopause-map-to-brain-aging-and-dementia-risk"
canonical_url: "https://medichelpline.com/clinical-feed/nature-2-blood-proteomics-of-menopause-map-to-brain-aging-and-dementia-risk"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "Nature Medicine"
source_url: "https://www.nature.com/articles/s41591-026-04648-4"
published_at: "2026-09-22T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Blood proteomics of menopause reveal links to brain aging and dementia risk
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-2-blood-proteomics-of-menopause-map-to-brain-aging-and-dementia-risk
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** Nature Medicine
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41591-026-04648-4)
- **Published At:** 2026-09-22T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The study used blood proteomics to identify molecular changes accompanying **menopause** and to map those changes to brain aging and dementia risk. - Initial discovery was performed in n = 80 rigorously staged (STRAW+10) premenopausal, perimenopausal and postmenopausal women aged 43–58 years using serum NULISAseq proteomics. - Spontaneous menopause was associated with dysregulation of inflammatory, synaptic, metabolic and **Alzheimer’s disease**–related biological processes; these proteomic changes tracked more strongly with hormone status than chronological age. - Validation in an independent, age-matched cohort (n = 2,814) using plasma Olink proteomics replicated the reported shifts and showed broader menopause-related upregulation of **inflammatory** and catabolic processes, and evidence of accelerated organ and cellular aging, including signatures consistent with **brain aging**. - In four additional independent cohorts of older women (average ages 60.7–72.1 years; total n = 11,925), higher menopause proteomic scores were consistently associated with measures of cognitive aging and increased **dementia** risk. - The authors propose that the molecular signatures identified around menopause could help prioritize biomarkers or therapeutic targets to support midlife brain health in women. - Methodological details such as exact protein panels, statistical models, effect sizes, cohort names and follow-up durations were not fully reported in the provided source text and therefore are not summarized here.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [nature medicine](https://www.nature.com/nm) 3. [articles](https://www.nature.com/nm/articles?type=article) 4. article Blood proteomics of menopause map to brain aging and dementia risk [ Download PDF ](https://www.nature.com/articles/s41591-026-04648-4.pdf) [ Download PDF ](https://www.nature.com/articles/s41591-026-04648-4.pdf) * Article * [Open access](https://www.springernature.com/gp/open-science/about/the-fundamentals-of-open-access-and-open-research) * Published: 22 September 2026 # Blood proteomics of menopause map to brain aging and dementia risk * [Madeline Wood Alexander](https://www.nature.com/articles/s41591-026-04648-4#auth-Madeline-Wood_Alexander-Aff1-Aff2-Aff3) [ORCID: orcid.org/0000-0003-4598-0201](https://orcid.org/0000-0003-4598-0201)[1](https://www.nature.com/articles/s41591-026-04648-4#Aff1),[2](https://www.nature.com/articles/s41591-026-04648-4#Aff2),[3](https://www.nature.com/articles/s41591-026-04648-4#Aff3), * [Jennifer S. Rabin](https://www.nature.com/articles/s41591-026-04648-4#auth-Jennifer_S_-Rabin-Aff1-Aff2-Aff3-Aff4) [ORCID: orcid.org/0000-0003-4754-2221](https://orcid.org/0000-0003-4754-2221)[1](https://www.nature.com/articles/s41591-026-04648-4#Aff1),[2](https://www.nature.com/articles/s41591-026-04648-4#Aff2),[3](https://www.nature.com/articles/s41591-026-04648-4#Aff3),[4](https://www.nature.com/articles/s41591-026-04648-4#Aff4), * [Michelle Caunca](https://www.nature.com/articles/s41591-026-04648-4#auth-Michelle-Caunca-Aff5)[5](https://www.nature.com/articles/s41591-026-04648-4#Aff5), * [Allesandra Iadipaolo](https://www.nature.com/articles/s41591-026-04648-4#auth-Allesandra-Iadipaolo-Aff6-Aff7-Aff8)[6](https://www.nature.com/articles/s41591-026-04648-4#Aff6),[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[8](https://www.nature.com/articles/s41591-026-04648-4#Aff8), * [Louisa Cornelis](https://www.nature.com/articles/s41591-026-04648-4#auth-Louisa-Cornelis-Aff9)[9](https://www.nature.com/articles/s41591-026-04648-4#Aff9), * [Ria Warrier](https://www.nature.com/articles/s41591-026-04648-4#auth-Ria-Warrier-Aff10)[10](https://www.nature.com/articles/s41591-026-04648-4#Aff10), * [Keenan A. Walker](https://www.nature.com/articles/s41591-026-04648-4#auth-Keenan_A_-Walker-Aff10) [ORCID: orcid.org/0000-0002-5989-9853](https://orcid.org/0000-0002-5989-9853)[10](https://www.nature.com/articles/s41591-026-04648-4#Aff10), * [Nina Miolane](https://www.nature.com/articles/s41591-026-04648-4#auth-Nina-Miolane-Aff7-Aff9)[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[9](https://www.nature.com/articles/s41591-026-04648-4#Aff9), * [Veronica Augustina Bot](https://www.nature.com/articles/s41591-026-04648-4#auth-Veronica_Augustina-Bot-Aff11-Aff12-Aff13) [ORCID: orcid.org/0009-0008-5060-1142](https://orcid.org/0009-0008-5060-1142)[11](https://www.nature.com/articles/s41591-026-04648-4#Aff11),[12](https://www.nature.com/articles/s41591-026-04648-4#Aff12),[13](https://www.nature.com/articles/s41591-026-04648-4#Aff13), * [Brendan Wood](https://www.nature.com/articles/s41591-026-04648-4#auth-Brendan-Wood-Aff1-Aff14)[1](https://www.nature.com/articles/s41591-026-04648-4#Aff1),[14](https://www.nature.com/articles/s41591-026-04648-4#Aff14), * [Hamilton Se-Hwee Oh](https://www.nature.com/articles/s41591-026-04648-4#auth-Hamilton_Se_Hwee-Oh-Aff15-Aff16-Aff17-Aff18) [ORCID: orcid.org/0000-0001-8192-7593](https://orcid.org/0000-0001-8192-7593)[15](https://www.nature.com/articles/s41591-026-04648-4#Aff15),[16](https://www.nature.com/articles/s41591-026-04648-4#Aff16),[17](https://www.nature.com/articles/s41591-026-04648-4#Aff17),[18](https://www.nature.com/articles/s41591-026-04648-4#Aff18), * [Tony Wyss-Coray](https://www.nature.com/articles/s41591-026-04648-4#auth-Tony-Wyss_Coray-Aff11-Aff12-Aff19) [ORCID: orcid.org/0000-0001-5893-0831](https://orcid.org/0000-0001-5893-0831)[11](https://www.nature.com/articles/s41591-026-04648-4#Aff11),[12](https://www.nature.com/articles/s41591-026-04648-4#Aff12),[19](https://www.nature.com/articles/s41591-026-04648-4#Aff19), * [Albert Pham](https://www.nature.com/articles/s41591-026-04648-4#auth-Albert-Pham-Aff20)[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20), * [Julia Borger](https://www.nature.com/articles/s41591-026-04648-4#auth-Julia-Borger-Aff20)[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20), * [Valentina Diaz](https://www.nature.com/articles/s41591-026-04648-4#auth-Valentina-Diaz-Aff20)[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20), * [Emily W. Paolillo](https://www.nature.com/articles/s41591-026-04648-4#auth-Emily_W_-Paolillo-Aff20)[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20), * [Joel Kramer](https://www.nature.com/articles/s41591-026-04648-4#auth-Joel-Kramer-Aff20)[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20), * [Laura Pritschet](https://www.nature.com/articles/s41591-026-04648-4#auth-Laura-Pritschet-Aff7-Aff21)[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[21](https://www.nature.com/articles/s41591-026-04648-4#Aff21), * [Caitlin Taylor](https://www.nature.com/articles/s41591-026-04648-4#auth-Caitlin-Taylor-Aff6-Aff7)[6](https://www.nature.com/articles/s41591-026-04648-4#Aff6),[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7), * [Matthew S. Panizzon](https://www.nature.com/articles/s41591-026-04648-4#auth-Matthew_S_-Panizzon-Aff22)[22](https://www.nature.com/articles/s41591-026-04648-4#Aff22), * [Ramiro Eduardo Rea Reyes](https://www.nature.com/articles/s41591-026-04648-4#auth-Ramiro_Eduardo-Rea_Reyes-Aff23)[23](https://www.nature.com/articles/s41591-026-04648-4#Aff23), * [Marisa N. Denkinger](https://www.nature.com/articles/s41591-026-04648-4#auth-Marisa_N_-Denkinger-Aff24)[24](https://www.nature.com/articles/s41591-026-04648-4#Aff24), * [Nicholas J. Ashton](https://www.nature.com/articles/s41591-026-04648-4#auth-Nicholas_J_-Ashton-Aff24-Aff25)[24](https://www.nature.com/articles/s41591-026-04648-4#Aff24),[25](https://www.nature.com/articles/s41591-026-04648-4#Aff25), * [Sterling C. Johnson](https://www.nature.com/articles/s41591-026-04648-4#auth-Sterling_C_-Johnson-Aff23-Aff26) [ORCID: orcid.org/0000-0002-8501-545X](https://orcid.org/0000-0002-8501-545X)[23](https://www.nature.com/articles/s41591-026-04648-4#Aff23),[26](https://www.nature.com/articles/s41591-026-04648-4#Aff26), * [Emily G. Jacobs](https://www.nature.com/articles/s41591-026-04648-4#auth-Emily_G_-Jacobs-Aff6-Aff7-Aff8) [ORCID: orcid.org/0000-0003-0001-5096](https://orcid.org/0000-0003-0001-5096)[6](https://www.nature.com/articles/s41591-026-04648-4#Aff6),[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[8](https://www.nature.com/articles/s41591-026-04648-4#Aff8), * [Rowan Saloner](https://www.nature.com/articles/s41591-026-04648-4#auth-Rowan-Saloner-Aff7-Aff20) [ORCID: orcid.org/0000-0002-1351-6183](https://orcid.org/0000-0002-1351-6183)[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20) [na1](https://www.nature.com/articles/s41591-026-04648-4#na1) & * … * [Kaitlin B. Casaletto](https://www.nature.com/articles/s41591-026-04648-4#auth-Kaitlin_B_-Casaletto-Aff7-Aff20) [ORCID: orcid.org/0000-0001-5000-7604](https://orcid.org/0000-0001-5000-7604)[7](https://www.nature.com/articles/s41591-026-04648-4#Aff7),[20](https://www.nature.com/articles/s41591-026-04648-4#Aff20) [na1](https://www.nature.com/articles/s41591-026-04648-4#na1) Show authors [_Nature Medicine_](https://www.nature.com/nm) (2026) [Cite this article](https://www.nature.com/articles/s41591-026-04648-4#citeas) [ Save article ](https://www.nature.com/articles/s41591-026-04648-4/save-research?_csrf=p1Gzt_tl1giZ6Bx8GyNzHiFmO8qnxvKM) [ View saved research ](https://www.nature.com/saved-research) ## 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. ### Explore related subjects Discover the latest articles and news in related subjects. * [Alzheimer's disease](https://www.nature.com/subjects/alzheimers-disease) * [Protein–protein interaction networks](https://www.nature.com/subjects/protein-protein-interaction-networks) * [Proteome informatics](https://www.nature.com/subjects/proteome-informatics) * [Risk factors](https://www.nature.com/subjects/risk-factors) ## Main Accumulating data point towards menopause as a critical inflection point in the aging process[1](https://www.nature.com/articles/s41591-026-04648-4#ref-CR1 "Levine, M. E. et al. Menopause accelerates biological aging. Proc. Natl Acad. Sci. USA 113, 9327–9332 https://doi.org/10.1073/pnas.1604558113 \(2016\)."). Universal to all midlife people with ovaries, menopause is characterized by a steep decline in ovarian hormones (17β-estradiol, progesterone) and a sustained rise in follicle-stimulating hormone (FSH). These endocrine shifts are associated with widespread multisystem health effects[1](https://www.nature.com/articles/s41591-026-04648-4#ref-CR1 "Levine, M. E. et al. Menopause accelerates biological aging. Proc. Natl Acad. Sci. USA 113, 9327–9332 https://doi.org/10.1073/pnas.1604558113 \(2016\)."),[2](https://www.nature.com/articles/s41591-026-04648-4#ref-CR2 "McCarthy, M. & Raval, A. P. The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease. J. Neuroinflammation 17, 317 https://doi.org/10.1186/s12974-020-01998-9 \(2020\)."),[3](https://www.nature.com/articles/s41591-026-04648-4#ref-CR3 "El Khoudary, S. R. et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association. Circulation 142, e506–e532 https://doi.org/10.1161/CIR.0000000000000912 \(2020\)."),[4](https://www.nature.com/articles/s41591-026-04648-4#ref-CR4 "Hara, Y., Waters, E. M., McEwen, B. S. & Morrison, J. H. Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol. Rev. 95, 785–807 https://doi.org/10.1152/physrev.00036.2014 \(2015\).") that may be relevant for later brain aging and dementia risk[5](https://www.nature.com/articles/s41591-026-04648-4#ref-CR5 "Wood Alexander, M. et al. The interplay between age at menopause and synaptic integrity on Alzheimer’s disease risk in women. Sci. Adv. 11, eadt0757 https://doi.org/10.1126/sciadv.adt0757 \(2025\)."),[6](https://www.nature.com/articles/s41591-026-04648-4#ref-CR6 "Coughlan, G. T. et al. Association of age at menopause and hormone therapy use with tau and β-amyloid positron emission tomography. JAMA Neurol. 80, 462–473 https://doi.org/10.1001/jamaneurol.2023.0455 \(2023\)."),[7](https://www.nature.com/articles/s41591-026-04648-4#ref-CR7 "Gong, J., Harris, K., Peters, S. A. E. & Woodward, M. Reproductive factors and the risk of incident dementia: a cohort study of UK Biobank participants. PLOS Med. 19, e1003955 https://doi.org/10.1371/journal.pmed.1003955 \(2022\)."),[8](https://www.nature.com/articles/s41591-026-04648-4#ref-CR8 "Wood Alexander, M. et al. Associations between age at menopause, vascular risk, and 3-year cognitive change in the Canadian longitudinal study on aging. Neurology 102, e209298 https://doi.org/10.1212/WNL.0000000000209298 \(2024\)."),[9](https://www.nature.com/articles/s41591-026-04648-4#ref-CR9 "Wood Alexander, M. et al. Sex differences in associations of Lewy body disease with Alzheimer’s disease and cognitive decline. Ann. Neurol. 98, 1014–1026 https://doi.org/10.1002/ana.27308 \(2025\)."). Canonical menopause symptoms, including vasomotor (that is, hot flashes, night sweats), sleep problems and mood and/or cognitive changes, are neurologic in origin, suggesting an acute neural response to the changing endocrine environment[10](https://www.nature.com/articles/s41591-026-04648-4#ref-CR10 "Thurston, R. C., Thomas, H. N., Castle, A. J. & Gibson, C. J. Menopause as a biological and psychological transition. Nat. Rev. Psychol. 4, 530–543 https://doi.org/10.1038/s44159-025-00463-9 \(2025\)."),[11](https://www.nature.com/articles/s41591-026-04648-4#ref-CR11 "Maki, P. M. & Thurston, R. C. Menopause and brain health: hormonal changes are only part of the story. Front. Neurol. 11, 562275 https://doi.org/10.3389/fneur.2020.562275 \(2020\)."),[12](https://www.nature.com/articles/s41591-026-04648-4#ref-CR12 "Gurvich, C., Spector, A. & Hickey, M. Advances in understanding of cognitive symptoms during menopause. Lancet Obst. Gynaecol. Womens Health 2, e335–e345 https://doi.org/10.1016/S3050-5038\(26\)00043-9 \(2026\)."). A recent review estimated that 26–95% of women experience cognitive symptoms during menopause (for example, word-finding, attentional difficulties) and finds that observational studies show overall subtle performance declines (especially in verbal learning and memory) that fall within normative expectations over the menopause transition[12](https://www.nature.com/articles/s41591-026-04648-4#ref-CR12 "Gurvich, C., Spector, A. & Hickey, M. Advances in understanding of cognitive symptoms during menopause. Lancet Obst. Gynaecol. Womens Health 2, e335–e345 https://doi.org/10.1016/S3050-5038\(26\)00043-9 \(2026\)."). Further, experimental data suggest that hypothalamic aging can precede and may causally trigger ovarian senescence, inducing menopause[13](https://www.nature.com/articles/s41591-026-0464
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