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| 001 | 140668 | ||
| 005 | 20250417115321.0 | ||
| 024 | 7 | _ | |a 10.1002/ana.25446 |2 doi |
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| 024 | 7 | _ | |a 0364-5134 |2 ISSN |
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| 100 | 1 | _ | |a Candelise, Niccolò |0 P:(DE-2719)9000041 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a Seeding variability of different alpha synuclein strains in synucleinopathies. |
| 260 | _ | _ | |a Hoboken, NJ |c 2019 |b Wiley-Blackwell |
| 264 | _ | 1 | |3 online |2 Crossref |b Wiley |c 2019-03-27 |
| 264 | _ | 1 | |3 print |2 Crossref |b Wiley |c 2019-05-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1744883555_17132 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Currently, the exact reasons why different α-synucleinopathies exhibit variable pathologies and phenotypes are still unknown. A potential explanation may be the existence of distinctive α-synuclein conformers or strains. Here, we intend to analyze the seeding activity of dementia with Lewy bodies (DLB) and Parkinson's disease (PD) brain-derived α-synuclein seeds by real-time quaking-induced conversion (RT-QuIC) and to investigate the structure and morphology of the α-synuclein aggregates generated by RT-QuIC.A misfolded α-synuclein-enriched brain fraction from frontal cortex and substantia nigra pars compacta tissue, isolated by several filtration and centrifugation steps, was subjected to α-synuclein/RT-QuIC analysis. Our study included neuropathologically well-characterized cases with DLB, PD, and controls (Ctrl). Biochemical and morphological analyses of RT-QuIC products were conducted by western blot, dot blot analysis, Raman spectroscopy, atomic force microscopy, and transmission electron microscopy.Independently from the brain region, we observed different seeding kinetics of α-synuclein in the RT-QuIC in patients with DLB compared to PD and Ctrl. Biochemical characterization of the RT-QuIC product indicated the generation of a proteinase K-resistant and fibrillary α-synuclein species in DLB-seeded reactions, whereas PD and control seeds failed in the conversion of wild-type α-synuclein substrate.Structural variances of α-synuclein seeding kinetics and products in DLB and PD indicated, for the first time, the existence of different α-synuclein strains in these groups. Therefore, our study contributes to a better understanding of the clinical heterogeneity among α-synucleinopathies, offers an opportunity for a specific diagnosis, and opens new avenues for the future development of strain-specific therapies. Ann Neurol 2019;85:691-703. |
| 536 | _ | _ | |a 344 - Clinical and Health Care Research (POF3-344) |0 G:(DE-HGF)POF3-344 |c POF3-344 |f POF III |x 0 |
| 542 | _ | _ | |i 2019-03-27 |2 Crossref |u http://onlinelibrary.wiley.com/termsAndConditions#vor |
| 542 | _ | _ | |i 2019-03-27 |2 Crossref |u http://doi.wiley.com/10.1002/tdm_license_1.1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 2 | |a Aged |2 MeSH |
| 650 | _ | 2 | |a Aged, 80 and over |2 MeSH |
| 650 | _ | 2 | |a Brain: metabolism |2 MeSH |
| 650 | _ | 2 | |a Brain: pathology |2 MeSH |
| 650 | _ | 2 | |a Brain Chemistry: physiology |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Protein Isoforms: analysis |2 MeSH |
| 650 | _ | 2 | |a Protein Isoforms: metabolism |2 MeSH |
| 650 | _ | 2 | |a Spectrum Analysis, Raman: methods |2 MeSH |
| 650 | _ | 2 | |a Synucleinopathies: metabolism |2 MeSH |
| 650 | _ | 2 | |a Synucleinopathies: pathology |2 MeSH |
| 650 | _ | 2 | |a alpha-Synuclein: analysis |2 MeSH |
| 650 | _ | 2 | |a alpha-Synuclein: metabolism |2 MeSH |
| 700 | 1 | _ | |a Schmitz, Matthias |0 P:(DE-2719)9000287 |b 1 |e Corresponding author |u dzne |
| 700 | 1 | _ | |a Llorens, Franc |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Villar-Piqué, Anna |0 P:(DE-2719)9000327 |b 3 |u dzne |
| 700 | 1 | _ | |a Cramm, Maria |0 P:(DE-2719)2810657 |b 4 |u dzne |
| 700 | 1 | _ | |a Thom, Tobias |0 P:(DE-2719)9000851 |b 5 |u dzne |
| 700 | 1 | _ | |a Silva-Correia, Susana |0 P:(DE-2719)9000766 |b 6 |u dzne |
| 700 | 1 | _ | |a da Cunha, José Eriton Gomes |b 7 |
| 700 | 1 | _ | |a Möbius, Wiebke |b 8 |
| 700 | 1 | _ | |a Outeiro, Tiago F |0 P:(DE-HGF)0 |b 9 |
| 700 | 1 | _ | |a Álvarez, Valentina González |b 10 |
| 700 | 1 | _ | |a Banchelli, Martina |b 11 |
| 700 | 1 | _ | |a D'Andrea, Cristiano |b 12 |
| 700 | 1 | _ | |a de Angelis, Marella |b 13 |
| 700 | 1 | _ | |a Zafar, Saima |0 P:(DE-2719)9000358 |b 14 |u dzne |
| 700 | 1 | _ | |a Rabano, Alberto |b 15 |
| 700 | 1 | _ | |a Matteini, Paolo |b 16 |
| 700 | 1 | _ | |a Zerr, Inga |0 P:(DE-2719)2000058 |b 17 |e Last author |u dzne |
| 773 | 1 | 8 | |a 10.1002/ana.25446 |b : Wiley, 2019-03-27 |n 5 |p 691-703 |3 journal-article |2 Crossref |t Annals of Neurology |v 85 |y 2019 |x 0364-5134 |
| 773 | _ | _ | |a 10.1002/ana.25446 |g Vol. 85, no. 5, p. 691 - 703 |0 PERI:(DE-600)2037912-2 |n 5 |q 85:5<691 - 703 |p 691-703 |t Annals of neurology |v 85 |y 2019 |x 0364-5134 |
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