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According to a new hypothesis of distinct \u03b1\u2010synuclein spreading directions based on the initial site of pathology, the \u201cbrain\u2010first\u201d spreading subtype would be associated with a more asymmetric cerebral and nigrostriatal pathology than the \u201cbody\u2010first\u201d subtype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Here, we tested if proposed markers of brain\u2010first PD (ie, higher dopamine transporter [DaT] asymmetry; absence of rapid eye movement sleep behavior disorder [RBD]) are associated with a greater or more asymmetric reduction in gray matter volume (GMV) in comparison to body\u2010first PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data of 255 de novo PD patients and 110 healthy controls (HCs) were retrieved from the Parkinson's Progression Markers Initiative. Structural magnetic resonance images were preprocessed, and GMVs and their hemispherical asymmetry were obtained for each of the neuropathologically defined Braak stages. Group and correlation comparisons were performed to assess differences in GMV and GMV asymmetry between PD subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD patients demonstrated significantly smaller bilateral GMVs compared to HCs, in a pattern denoting stage\u2010dependent disease\u2010related brain atrophy. However, the degree of putaminal DaT asymmetry was not associated with reduced GMV or higher GMV asymmetry. Furthermore, RBD\u2010negative and RBD\u2010positive patients did not demonstrate a significant difference in GMV or GMV asymmetry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that putative brain\u2010first and body\u2010first patients do not present diverging brain atrophy patterns. Although certainly not disproving the brain\u2010first\/body\u2010first spreading hypothesis, this study fails to provide evidence in support of it. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29172","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T06:50:32Z","timestamp":1660027832000},"page":"2066-2074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Gray Matter Volume Loss in Proposed <scp>Brain\u2010First<\/scp> and <scp>Body\u2010First<\/scp> Parkinson's Disease Subtypes"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-9973","authenticated-orcid":false,"given":"Magdalena","family":"Banwinkler","sequence":"first","affiliation":[{"name":"Faculty of Medicine and 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of Cologne  Cologne Germany"},{"name":"Institute for Neuroscience and Medicine II, Molecular Organization of the Brain Research Center Juelich  Juelich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-2325","authenticated-orcid":false,"given":"Thilo","family":"van Eimeren","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine University of Cologne  Cologne Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Department of Neurology University of Cologne  Cologne 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