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To address this need, we examine sex differences in whole brain signatures of neurodegeneration due to aSyn toxicity in the M83 mouse model using longitudinal magnetic resonance imaging (MRI; T1-weighted; 100 \u03bcm\n                    <jats:sup>3<\/jats:sup>\n                    isotropic voxel; -7, 30, 90 and 120 days post-injection [dpi]; n\u2009\u2265\u20098 mice\/group\/sex\/time point). To initiate aSyn spreading, M83 mice are inoculated with recombinant human aSyn preformed fibrils (Hu-PFF) or phosphate buffered saline in the right striatum. We observe more aggressive neurodegenerative profiles over time for male Hu-PFF-injected mice when examining voxel-wise trajectories. However, at 90 dpi, we observe widespread patterns of neurodegeneration in the female Hu-PFF-injected mice. These differences are not accompanied by any differences in motor symptom onset between the sexes. However, male Hu-PFF-injected mice reached their humane endpoint sooner. These findings suggest that post-motor symptom onset, despite accelerated disease trajectories for male Hu-PFF-injected mice, neurodegeneration may appear sooner in the female Hu-PFF-injected mice (prior to motor symptomatology). These findings suggest that sex-specific synucleinopathy phenotypes urgently need to be considered to improve our understanding of neuroprotective and neurodegenerative mechanisms.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-07680-1","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T09:24:22Z","timestamp":1740216262000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Female mice exhibit resistance to disease progression despite early pathology in a transgenic mouse model inoculated with alpha-synuclein fibrils"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4608-3000","authenticated-orcid":false,"given":"Stephanie","family":"Tullo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3198-9736","authenticated-orcid":false,"given":"Janice Sung Hyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gallino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie","family":"Mar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Novikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1167-2513","authenticated-orcid":false,"given":"Rodrigo","family":"Sandoval Contreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raihaan","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-944X","authenticated-orcid":false,"given":"Esther","family":"del Cid-Pellitero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5520-6239","authenticated-orcid":false,"given":"Edward A.","family":"Fon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-9615","authenticated-orcid":false,"given":"Wen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-268X","authenticated-orcid":false,"given":"Irina","family":"Shlaifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Durcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-5778","authenticated-orcid":false,"given":"Marco A. 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