{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:18:40Z","timestamp":1787818720739,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":223,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Oxford Health Biomedical Research Centre","award":["NIHR203316"],"award-info":[{"award-number":["NIHR203316"]}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203311"],"award-info":[{"award-number":["NIHR203311"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Oxford Health Clinical Research Facility"},{"DOI":"10.13039\/100032631","name":"Calico Life Sciences LLC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032631","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre for Integrative Neuroimaging"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203139\/Z\/16\/Z"],"award-info":[{"award-number":["203139\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203139\/A\/16\/Z"],"award-info":[{"award-number":["203139\/A\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Men are more likely than women to develop Parkinson\u2019s disease, yet the biological basis of this sex difference in Parkinson\u2019s disease risk remains unresolved. The nigrosome-1 (NG-1), a dopaminergic subregion of the substantia nigra, is selectively vulnerable to degeneration and iron accumulation in Parkinson\u2019s disease, therefore representing a plausible locus for sex-linked vulnerability. Using iron-sensitive magnetic resonance imaging from the UK Biobank, we examined sex differences in NG-1 magnetic susceptibility across adulthood. We analysed cross-sectional data from 53 792 individuals aged 45\u201385 years and longitudinal follow-up in 4068 participants. Across mid-to-late adulthood, men consistently exhibited higher NG-1 magnetic susceptibility than women, suggestive of greater iron-related signal burden. In contrast, age-related trajectories and rates of within-person change were similar between sexes, with no evidence for accelerated nigrostriatal ageing in men. Sensitivity analyses showed that these sex differences were not substantially modified by genetic risk for Parkinson\u2019s disease, cardiometabolic disease or major lifestyle factors. Together, these findings suggest that sex differences in NG-1 susceptibility are expressed primarily as a stable baseline offset rather than divergent ageing dynamics. By distinguishing baseline variation from age-related changes in a selectively vulnerable dopaminergic system, this study provides population-scale evidence relevant to understanding sex differences in vulnerability to Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag310","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:34:31Z","timestamp":1786448071000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex-dependent dopaminergic vulnerability may contribute to sex differences in Parkinson\u2019s disease risk"],"prefix":"10.1093","volume":"8","author":[{"given":"Tamir","family":"Eisenstein","sequence":"first","affiliation":[{"name":"Oxford Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Division of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J","family":"Lange","sequence":"additional","affiliation":[{"name":"Oxford Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-5841","authenticated-orcid":false,"given":"Michele T M","family":"Hu","sequence":"additional","affiliation":[{"name":"Oxford Parkinson\u2019s Disease Centre, Division of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-2801","authenticated-orcid":false,"given":"Johannes C","family":"Klein","sequence":"additional","affiliation":[{"name":"Oxford Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Division of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"10423","key":"2026082703465765200_fcag310-B1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0140-6736(23)01419-8","article-title":"The epidemiology of Parkinson\u2019s disease","volume":"403","author":"Ben-Shlomo","year":"2024","journal-title":"Lancet (London, England)"},{"key":"2026082703465765200_fcag310-B2","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for prevalence of Parkinson\u2019s disease and its driving factors in 195 countries and territories to 2050: Modelling study of global burden of disease study 2021","volume":"388","author":"Su","year":"2025","journal-title":"BMJ"},{"key":"2026082703465765200_fcag310-B3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.yfrne.2017.09.002","article-title":"Sex differences in Parkinson\u2019s disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics","volume":"50","author":"Jurado-Coronel","year":"2018","journal-title":"Front Neuroendocrinol"},{"issue":"Pt 5","key":"2026082703465765200_fcag310-B4","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","article-title":"Ageing and Parkinson\u2019s disease: Substantia nigra regional selectivity","volume":"114","author":"Fearnley","year":"1991","journal-title":"Brain"},{"issue":"3","key":"2026082703465765200_fcag310-B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/BF01244786","article-title":"Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain","volume":"74","author":"Sofic","year":"1988","journal-title":"J Neural Transm"},{"issue":"1","key":"2026082703465765200_fcag310-B6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41531-018-0047-3","article-title":"Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson\u2019s disease","volume":"4","author":"Sulzer","year":"2018","journal-title":"NPJ Parkinsons Dis"},{"issue":"8","key":"2026082703465765200_fcag310-B7","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/brain\/122.8.1421","article-title":"The substantia nigra of the human brain: I. Nigrosomes and the nigral matrix, a compartmental organization based on calbindin D28K immunohistochemistry","volume":"122","author":"Damier","year":"1999","journal-title":"Brain"},{"issue":"Pt 8","key":"2026082703465765200_fcag310-B8","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/brain\/122.8.1437","article-title":"The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson\u2019s disease","volume":"122","author":"Damier","year":"1999","journal-title":"Brain"},{"key":"2026082703465765200_fcag310-B9","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroimage.2024.120547","article-title":"Neuroimaging of Parkinson\u2019s disease by quantitative susceptibility mapping","volume":"289","author":"Guan","year":"2024","journal-title":"Neuroimage"},{"issue":"4","key":"2026082703465765200_fcag310-B10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093814","article-title":"The \u2018swallow tail\u2019 appearance of the healthy nigrosome\u2014A new accurate test of Parkinson\u2019s disease: A case-control and retrospective cross-sectional MRI study at 3T","volume":"9","author":"Schwarz","year":"2014","journal-title":"PLoS One"},{"key":"2026082703465765200_fcag310-B11","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.nicl.2018.05.027","article-title":"Parkinson\u2019s disease related signal change in the nigrosomes 1\u20135 and the substantia nigra using T2* weighted 7T MRI","volume":"19","author":"Schwarz","year":"2018","journal-title":"NeuroImage Clin"},{"issue":"1","key":"2026082703465765200_fcag310-B12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41531-025-00972-7","article-title":"High-resolution mapping of substantia nigra in Parkinson\u2019s disease using 7 tesla magnetic resonance imaging","volume":"11","author":"Madelung","year":"2025","journal-title":"NPJ Parkinsons Dis"},{"key":"2026082703465765200_fcag310-B13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.parkreldis.2020.07.002","article-title":"Diagnostic accuracy of the appearance of nigrosome-1 on magnetic resonance imaging in Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"78","author":"Chau","year":"2020","journal-title":"Parkinsonism Relat Disord"},{"issue":"6","key":"2026082703465765200_fcag310-B14","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1212\/WNL.0b013e31829e6fd2","article-title":"Visualization of nigrosome 1 and its loss in PD: Pathoanatomical correlation and in vivo 7 T MRI","volume":"81","author":"Blazejewska","year":"2013","journal-title":"Neurology"},{"issue":"3","key":"2026082703465765200_fcag310-B15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0014-5793(01)03269-0","article-title":"The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson\u2019s disease","volume":"510","author":"Zecca","year":"2002","journal-title":"FEBS Lett"},{"issue":"11","key":"2026082703465765200_fcag310-B16","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1002\/mds.27502","article-title":"Life span pigmentation changes of the substantia nigra detected by neuromelanin-sensitive MRI","volume":"33","author":"Xing","year":"2018","journal-title":"Mov Disord"},{"issue":"9","key":"2026082703465765200_fcag310-B17","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/sj.jcbfm.9600276","article-title":"Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease","volume":"26","author":"Bohnen Nicolaas","year":"2006","journal-title":"J Cereb Blood Flow Metab"},{"issue":"4","key":"2026082703465765200_fcag310-B18","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1016\/j.neurobiolaging.2015.01.016","article-title":"Effects of aging and gender on striatal and extrastriatal [123I]FP-CIT binding in Parkinson\u2019s disease","volume":"36","author":"Kaasinen","year":"2015","journal-title":"Neurobiol Aging"},{"issue":"1","key":"2026082703465765200_fcag310-B19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuroimage.2007.11.017","article-title":"Age, gender, and hemispheric differences in iron deposition in the human brain: An in vivo MRI study","volume":"40","author":"Xu","year":"2008","journal-title":"Neuroimage"},{"key":"2026082703465765200_fcag310-B20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.neuroimage.2015.07.050","article-title":"Age and sex related differences in subcortical brain iron concentrations among healthy adults","volume":"122","author":"Persson","year":"2015","journal-title":"Neuroimage"},{"key":"2026082703465765200_fcag310-B21","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.neuroimage.2014.11.010","article-title":"Validation of quantitative susceptibility mapping with Perls\u2019 iron staining for subcortical gray matter","volume":"105","author":"Sun","year":"2015","journal-title":"Neuroimage"},{"key":"2026082703465765200_fcag310-B22","volume-title":"Definitions of Parkinson\u2019s disease and the Major causes of parkinsonism, UK biobank phase 1 outcomes adjudication","author":"Bush","year":"2018"},{"key":"2026082703465765200_fcag310-B23","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neuroimage.2017.10.034","article-title":"Image processing and quality control for the first 10,000 brain imaging datasets from UK biobank","volume":"166","author":"Alfaro-Almagro","year":"2018","journal-title":"Neuroimage"},{"issue":"6","key":"2026082703465765200_fcag310-B24","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41593-022-01074-w","article-title":"Phenotypic and genetic associations of quantitative magnetic susceptibility in UK biobank brain imaging","volume":"25","author":"Wang","year":"2022","journal-title":"Nat Neurosci"},{"key":"2026082703465765200_fcag310-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1162\/imag_a_00100","article-title":"MMORF\u2014FSL\u2019s MultiMOdal registration framework","volume":"2","author":"Lange","year":"2024","journal-title":"Imaging Neurosci"},{"issue":"1","key":"2026082703465765200_fcag310-B26","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41597-025-05325-w","article-title":"High resolution multi-parametric probabilistic in vivo atlas of dorsolateral nigral hyperintensity via 7T MRI","volume":"12","author":"Lancione","year":"2025","journal-title":"Sci Data"},{"issue":"42","key":"2026082703465765200_fcag310-B27","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2510486122","article-title":"Sex differences in healthy brain aging are unlikely to explain higher Alzheimer\u2019s disease prevalence in women","volume":"122","author":"Ravndal","year":"2025","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082703465765200_fcag310-B28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"2026082703465765200_fcag310-B29","doi-asserted-by":"crossref","DOI":"10.1016\/j.nicl.2019.102103","article-title":"Imaging the nigrosome 1 in the substantia nigra using susceptibility weighted imaging and quantitative susceptibility mapping: An application to Parkinson\u2019s disease","volume":"25","author":"Cheng","year":"2020","journal-title":"NeuroImage Clin"},{"issue":"1","key":"2026082703465765200_fcag310-B30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.neuron.2024.12.005","article-title":"Biological sex matters in brain aging","volume":"113","author":"Dubal","year":"2025","journal-title":"Neuron"},{"issue":"20","key":"2026082703465765200_fcag310-B31","article-title":"Mapping human brain charts cross-sectionally and longitudinally","volume":"120","author":"Di Biase","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"2026082703465765200_fcag310-B32","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal trends in the prevalence of Parkinson\u2019s disease from 1980 to 2023: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Heal Longev"},{"key":"2026082703465765200_fcag310-B33","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.nicl.2016.11.015","article-title":"9.4T MR microscopy of the substantia nigra with pathological validation in controls and disease","volume":"13","author":"Massey","year":"2017","journal-title":"NeuroImage Clin"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcag310\/70616267\/fcag310.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/4\/fcag310\/70616267\/fcag310.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/4\/fcag310\/70616267\/fcag310.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:47:07Z","timestamp":1787816827000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcag310\/8759393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcag310","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"fcag310"}}