{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T06:27:04Z","timestamp":1786775224658,"version":"build-2736575974"},"reference-count":93,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010169042"],"award-info":[{"award-number":["PJT\u2010169042"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Conformationally distinct \u201cstrains\u201d of \u03b1\u2010synuclein aggregates are believed to contribute to the clinical and pathological diversity observed among synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease. Cases of MSA can be classified into two distinct subtypes: the cerebellar variant, MSA\u2010C, and the parkinsonian variant, MSA\u2010P, as determined by differences in their clinical and\/or neuropathological presentations. To assess whether distinct \u03b1\u2010synuclein strains may be present in individuals with MSA\u2010C versus MSA\u2010P, we characterized the conformational and seeding properties of \u03b1\u2010synuclein aggregates in various brain regions from MSA\u2010C and MSA\u2010P patients and performed propagation studies in M83 transgenic mice. Biochemical fingerprinting of \u03b1\u2010synuclein aggregates using limited proteolysis and a conformational stability assay failed to reveal differences between MSA\u2010C and MSA\u2010P either before or after propagation in mice. Similarly, using brain extracts from either MSA patients or MSA\u2010inoculated mice, MSA\u2010C and MSA\u2010P \u03b1\u2010synuclein aggregates exhibited indistinguishable seeding attributes in a seed amplification assay. Finally, no differences were observed in either the kinetics of disease progression or the extent of cerebral \u03b1\u2010synuclein deposition in M83 mice inoculated with either MSA\u2010C or MSA\u2010P, regardless of the brain region from which the injected \u03b1\u2010synuclein aggregates were derived. These results suggest that MSA subtypes are unlikely to arise because of distinct \u03b1\u2010synuclein strains. Instead, our findings support a model in which the same \u03b1\u2010synuclein strain initially forms in different brain regions, leading to differences in disease manifestation.<\/jats:p>","DOI":"10.1111\/bpa.70134","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T05:55:46Z","timestamp":1786773346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1\u2010Synuclein strain homogeneity in multiple system atrophy subtypes"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-6187","authenticated-orcid":false,"given":"Heather H. 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