{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:00:35Z","timestamp":1777356035014,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Neurology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Earlier menopause is a risk factor for several age-related diseases, including dementia. The biological pathways linking menopause timing to later-life brain aging are not understood. Leveraging large-scale plasma proteomics in postmenopausal women from the UK Biobank (\n                  <jats:italic>N<\/jats:italic>\n                  =15,012), earlier menopause was associated with upregulation of pro-inflammatory and extracellular matrix degradation pathways, plus accelerated aging across proteomic clocks of organ and cellular aging, including brain and oligodendrocyte aging. Elevated GDF15, a canonical aging marker, was the top protein correlate of earlier menopause. We observed robust replication of menopause timing proteomic shifts in the Women\u2019s Health Initiative Long Life Study (\n                  <jats:italic>N<\/jats:italic>\n                  =1,210). In UKB, proteins associated with earlier menopause, including GDF15, exhibited concordant associations with incident dementia risk and brain atrophy, cerebral small vessel disease burden, and white matter microstructural integrity. Collectively, our findings identify proteomic signatures linking ovarian aging to brain aging, providing a framework to inform interventions to reduce dementia risk.\n                <\/jats:p>","DOI":"10.64898\/2026.04.23.26351500","type":"posted-content","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:40:15Z","timestamp":1777066815000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma proteomics link menopause timing to brain aging and dementia risk"],"prefix":"10.64898","author":[{"given":"Madeline Wood","family":"Alexander","sequence":"first","affiliation":[{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada"},{"name":"Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Wood","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-7593","authenticated-orcid":false,"given":"Hamilton See-Hwee","family":"Oh","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Brain and Body Research Center of the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. 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