{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:22:50Z","timestamp":1788340970080,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuroprotection"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) involves progressive gray matter (GM) atrophy, but stage\u2010specific imaging patterns and their genetic mechanisms remain unclear. This study aimed to characterize GM atrophy across PD stages and link these patterns to transcriptional profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 542 patients with PD were obtained from the Parkinson's Progression Markers Initiative (PPMI) database, including early\u2010stage (&lt;2.5 years,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009192), mid\u2010stage (2.5\u20135.0 years,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009235), and late\u2010stage (&gt;5.0 years,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009115). Structural magnetic resonance imaging data underwent voxel\u2010based morphometry analysis and group differences were assessed using voxel\u2010wise two\u2010sample\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests with age, sex, and total intracranial volume as covariates, followed by correlation analyses between significant GM clusters and clinical features. Gene expression data from Allen Human Brain Atlas (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.brain-map.org\">http:\/\/www.brain-map.org<\/jats:ext-link>\n                      ) were spatially mapped to imaging patterns with gene\u2010wise Pearson's correlations, as well as a series of enrichment, tissue\u2010specific, and disease\u2010association analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to early\u2010stage PD, the mid\u2010stage showed brain GM atrophy in brain regions such as the right angular gyrus, superior temporal gyrus, and middle frontal gyrus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05, cluster\u2010level FWE correction). As PD progressed to the late stage, GM atrophy expanded to the left angular gyrus, left temporal pole, middle occipital gyrus, and bilateral posterior cingulate gyrus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05, cluster\u2010level FWE correction). Transcriptomic analyses identified 1262 shared genes across all stages, 1222 early\u2010mid\u2010stage\u2010specific genes, and 1847 mid\u2010late\u2010stage\u2010specific genes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05, FWE correction). Gene enrichment analysis showed that the three gene sets shared 13 cellular components and 10 biological processes that were enriched in common expression pathways, presenting both shared and specific functional changes at different stages of PD progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Progressive GM atrophy in PD reflects coordinated but stage\u2010differentiated molecular processes, revealing cellular and genetic architectures underlying disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nep3.70040","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:52:25Z","timestamp":1781502745000},"page":"262-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imaging patterns and genetic associations of brain atrophy across distinct symptom stages in Parkinson's disease"],"prefix":"10.1002","volume":"4","author":[{"given":"Yi","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liujia","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2241-9227","authenticated-orcid":false,"given":"Yachen","family":"Shi","sequence":"additional","affiliation":[{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"},{"name":"Department of Neurology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangming","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Affiliated Wuxi People\u2032s Hospital of Nanjing Medical University Wuxi Jiangsu China"},{"name":"Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00218-X"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"46","article-title":"Where do we stand on neuroprotection? 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