{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:05:01Z","timestamp":1790553901005,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We investigated \u03b1-synuclein\u2019s (\u03b1Syn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic \u03b1Syn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson\u2019s disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant \u03b1Syn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson\u2019s disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric \u03b1Syn into fibrillar assemblies. Significant variations in the characteristics of fibrillar assemblies derived from different regions even within the same individual were observed. This finding suggests that fixation stabilizes seeds with an otherwise limited seeding propensity, that yield assemblies with different intrinsic structures (i.e., strains). The lag phase preceding fibril assembly for patients \u226580 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic \u03b1Syn with time. Seeding activity did not diminish in late-stage disease. No statistically significant difference in the seeding efficiency of specific regions was found, nor was there a relationship between seeding efficiency and the load of pathogenic \u03b1Syn in a particular region at a given neuropathological stage.<\/jats:p>","DOI":"10.3390\/cells10010139","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T14:28:53Z","timestamp":1610461733000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Seeding Propensity and Characteristics of Pathogenic \u03b1Syn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Alexis","family":"Fenyi","sequence":"first","affiliation":[{"name":"Institute Francois Jacob (MIRCen), CEA and Laboratory of Neurodegenerative Diseases, CNRS, 92265 Fontenay-Aux-Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Duyckaerts","sequence":"additional","affiliation":[{"name":"Laboratoire de Neuropathologie Escourolle, H\u00f4pital de la Salp\u00eatri\u00e8re, AP-HP, &amp; Alzheimer Prion Team, ICM, 47 Bd de l\u2019H\u00f4pital, 75651 CEDEX 13 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Bousset","sequence":"additional","affiliation":[{"name":"Institute Francois Jacob (MIRCen), CEA and Laboratory of Neurodegenerative Diseases, CNRS, 92265 Fontenay-Aux-Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-1045","authenticated-orcid":false,"given":"Heiko","family":"Braak","sequence":"additional","affiliation":[{"name":"Clinical Neuroanatomy Section\/Department of Neurology, Center for Biomedical Research, University of Ulm, Helmholtzstra\u00dfe 8\/1, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-7838","authenticated-orcid":false,"given":"Kelly","family":"Del Tredici","sequence":"additional","affiliation":[{"name":"Clinical Neuroanatomy Section\/Department of Neurology, Center for Biomedical Research, University of Ulm, Helmholtzstra\u00dfe 8\/1, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Melki","sequence":"additional","affiliation":[{"name":"Institute Francois Jacob (MIRCen), CEA and Laboratory of Neurodegenerative Diseases, CNRS, 92265 Fontenay-Aux-Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Brainbank Neuro-CEB Neuropathology Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","article-title":"Idiopathic Parkinson\u2019s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen","volume":"110","author":"Braak","year":"2003","journal-title":"J. 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