Blood proteomics of menopause map to brain aging and dementia risk

IF 52.5 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Medicine Pub Date : 2026-09-22 DOI:10.1038/s41591-026-04648-4

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,Kaitlin B. Casaletto

{"title":"Blood proteomics of menopause map to brain aging and dementia risk","authors":"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,Kaitlin B. Casaletto","doi":"10.1038/s41591-026-04648-4","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"10 1","pages":""},"PeriodicalIF":52.5000,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41591-026-04648-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

绝经期血液蛋白质组学与脑老化和痴呆风险相关

更年期是生物衰老的一个标志性过程，与后期神经退行性风险有关，但这种联系的潜在途径尚不清楚。在这里，我们使用来自几个队列的血液蛋白质组学数据来确定与更年期相关的生物学变化及其与脑衰老的联系。在n = 80严格分期（STRAW+10）绝经前、围绝经期和绝经后妇女（43-58岁）的血清NULISAseq蛋白质组学研究中，我们发现自发性绝经的特征是炎症、突触、代谢和阿尔茨海默病生物学过程的失调，这些过程与激素的关系比与年龄的关系更密切。在年龄匹配的绝经前/围绝经期和绝经后妇女（n = 2,814）中，血浆Olink蛋白质组学验证分析重复了观察到的蛋白质组学变化，并揭示了更广泛的绝经相关炎症和分解代谢过程上调，以及器官和细胞衰老加速，包括脑衰老。在四个独立的老年妇女队列（平均年龄60.7-72.1岁；总n = 11925）中，较高的绝经期蛋白质组学评分与认知老化和痴呆风险一致相关。更年期的分子特征可能为中年妇女脑健康的生物标志物或治疗靶点的选择提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Medicine 医学-生化与分子生物学

CiteScore

100.90

自引率

0.70%

发文量

525

审稿时长

1 months

期刊介绍： Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.