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PD-associated \u03b1Syn (\u03b1Syn<jats:sup>PD<\/jats:sup>) aggregates can act as proteinaceous nuclei (\u201cseeds\u201d) able of self-templated propagation. Since this is strikingly reminiscent to properties of proteinaceous infectious particles (prions), lessons learned from prion diseases suggest to test whether transferred \u03b1Syn<jats:sup>PD<\/jats:sup> can propagate and induce neurological impairments or disease in a new host. Two studies that addressed this question provided divergent results. Intracerebral (i.c.) injection of Lewy body extracts from PD patients caused cerebral \u03b1Syn pathology, as well as nigrostriatal neurodegeneration, of wild-type mice and macaques, with the mice also showing motor impairments (Recasens et al. 2014, Ann Neurol 75:351\u2013362). In contrast, i.c. transmission of homogenates from PD brains did not stimulate, after \u201c&gt;\u2009360\u201d days post-injection (dpi), pathological \u03b1Syn conversion or clinical symptoms in transgenic TgM83<jats:sup>+\/\u2212<\/jats:sup> mice hemizygously expressing mutated (A53T) human \u03b1Syn (Prusiner et al. 2015, PNAS 112:E5308\u2013E5317). To advance the assessment of possible \u03b1Syn<jats:sup>PD<\/jats:sup> hazards by providing further data, we examined neuropathological and clinical effects upon i.c. transmission of brain, stomach wall and muscle tissue as well as blood from PD patients in TgM83<jats:sup>+\/\u2212<\/jats:sup> mice up to 612 dpi. This revealed a subtle, yet distinctive stimulation of localized \u03b1Syn aggregation in the somatodendritic compartment and dystrophic neurites of individual or focally clustered cerebral neurons after challenge with brain and stomach wall homogenates. No such effect was observed with transmitted blood or homogenized muscle tissue. The detected stimulation of \u03b1Syn aggregation was not accompanied by apparent motor impairments or overt neurological disease in TgM83<jats:sup>+\/\u2212<\/jats:sup> mice. Our study substantiated that transmitted \u03b1Syn<jats:sup>PD<\/jats:sup> seeds, including those from the stomach wall, are able to propagate in new mammalian hosts. The consequences of such propagation and potential safeguards need to be further investigated.<\/jats:p>","DOI":"10.1007\/s00401-021-02312-4","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T08:18:25Z","timestamp":1619338705000},"page":"861-879","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Transmissible \u03b1-synuclein seeding activity in brain and stomach of patients with Parkinson\u2019s disease"],"prefix":"10.1007","volume":"141","author":[{"given":"Achim","family":"Thomzig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Wagenf\u00fchr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Pinder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Joncic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Schulz-Schaeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6454-6657","authenticated-orcid":false,"given":"Michael","family":"Beekes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,24]]},"reference":[{"key":"2312_CR1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/531294a","volume":"531","author":"A Abbott","year":"2016","unstructured":"Abbott A (2016) The red-hot debate about transmissible Alzheimer\u2019s. 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