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Seeding 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 disease

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peer-reviewed

Erstveröffentlichung
2021-01-12
Authors
Fenyi, Alexis
Duyckaerts, Charles
Bousset, Luc
Braak, Heiko
Tredici, Kelly Del
et al.
Wissenschaftlicher Artikel


Published in
Cells ; 10 (2021), 1. - Art.-Nr. 139. - eISSN 2073-4409
Link to original publication
https://dx.doi.org/10.3390/cells10010139
Institutions
UKU. Klinik für Neurologie
Document version
published version (publisher's PDF)
Abstract
We 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.
Is supplemented by
https://www.mdpi.com/2073-4409/10/1/139/s1
Subject headings
[GND]: Synuclein <alpha-> | Parkinson-Krankheit | Lewy-Körperchen-Demenz | Prion | Darmwandnervensystem
[MeSH]: Synucleinopathies | Lewy body disease | Parkinson disease | alpha-Synuclein | Prions
[Free subject headings]: alpha-synuclein | enteric nervous system | incidental Lewy body disease | Parkinson’s disease | protein misfolding cyclic amplification (PMCA) | prion-like | synucleinopathy | synuclein strains
[DDC subject group]: DDC 610 / Medicine & health
License
CC BY 4.0 International
https://creativecommons.org/licenses/by/4.0/

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-43526

Fenyi, Alexis et al. (2022): Seeding 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 disease. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-43526
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