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AuthorFenyi, Alexisdc.contributor.author
AuthorDuyckaerts, Charlesdc.contributor.author
AuthorBousset, Lucdc.contributor.author
AuthorBraak, Heikodc.contributor.author
AuthorTredici, Kelly Deldc.contributor.author
AuthorMelki, Ronalddc.contributor.author
Authoron behalf of the Brainbank Neuro-CEB Neuropathology Network,dc.contributor.author
Date of accession2022-06-27T12:14:00Zdc.date.accessioned
Available in OPARU since2022-06-27T12:14:00Zdc.date.available
Date of first publication2021-01-12dc.date.issued
AbstractWe investigated α-synuclein’s (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson’s disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson’s disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric αSyn 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 ≥80 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic αSyn 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 αSyn in a particular region at a given neuropathological stage.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
Keywordalpha-synucleindc.subject
Keywordenteric nervous systemdc.subject
Keywordincidental Lewy body diseasedc.subject
KeywordParkinson’s diseasedc.subject
Keywordprotein misfolding cyclic amplification (PMCA)dc.subject
Keywordprion-likedc.subject
Keywordsynucleinopathydc.subject
Keywordsynuclein strainsdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHSynucleinopathiesdc.subject.mesh
MeSHLewy body diseasedc.subject.mesh
MeSHParkinson diseasedc.subject.mesh
MeSHalpha-Synucleindc.subject.mesh
MeSHPrionsdc.subject.mesh
TitleSeeding propensity and characteristics of pathogenic αSyn assemblies in formalin-fixed human tissue from the enteric nervous system, olfactory bulb, and brainstem in cases staged for Parkinson’s diseasedc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2021-02-03T19:04:24Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-43526dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-43602-1dc.identifier.urn
GNDSynuclein <alpha->dc.subject.gnd
GNDParkinson-Krankheitdc.subject.gnd
GNDLewy-Körperchen-Demenzdc.subject.gnd
GNDPriondc.subject.gnd
GNDDarmwandnervensystemdc.subject.gnd
InstitutionUKU. Klinik für Neurologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
DOI of original publication10.3390/cells10010139dc.relation1.doi
Source - Title of sourceCellssource.title
Source - Place of publicationMDPIsource.publisher
Source - Volume10source.volume
Source - Issue1source.issue
Source - Year2021source.year
Source - Article number139source.articleNumber
Source - eISSN2073-4409source.identifier.eissn
WoS000610006600001uulm.identifier.wos
Bibliographyuulmuulm.bibliographie
Is Supplemented Byhttps://www.mdpi.com/2073-4409/10/1/139/s1dc.relation.isSupplementedBy


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