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000140668 041__ $$aEnglish
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000140668 1001_ $$0P:(DE-2719)9000041$$aCandelise, Niccolò$$b0$$eFirst author$$udzne
000140668 245__ $$aSeeding variability of different alpha synuclein strains in synucleinopathies.
000140668 260__ $$aHoboken, NJ$$bWiley-Blackwell$$c2019
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000140668 520__ $$aCurrently, the exact reasons why different α-synucleinopathies exhibit variable pathologies and phenotypes are still unknown. A potential explanation may be the existence of distinctive α-synuclein conformers or strains. Here, we intend to analyze the seeding activity of dementia with Lewy bodies (DLB) and Parkinson's disease (PD) brain-derived α-synuclein seeds by real-time quaking-induced conversion (RT-QuIC) and to investigate the structure and morphology of the α-synuclein aggregates generated by RT-QuIC.A misfolded α-synuclein-enriched brain fraction from frontal cortex and substantia nigra pars compacta tissue, isolated by several filtration and centrifugation steps, was subjected to α-synuclein/RT-QuIC analysis. Our study included neuropathologically well-characterized cases with DLB, PD, and controls (Ctrl). Biochemical and morphological analyses of RT-QuIC products were conducted by western blot, dot blot analysis, Raman spectroscopy, atomic force microscopy, and transmission electron microscopy.Independently from the brain region, we observed different seeding kinetics of α-synuclein in the RT-QuIC in patients with DLB compared to PD and Ctrl. Biochemical characterization of the RT-QuIC product indicated the generation of a proteinase K-resistant and fibrillary α-synuclein species in DLB-seeded reactions, whereas PD and control seeds failed in the conversion of wild-type α-synuclein substrate.Structural variances of α-synuclein seeding kinetics and products in DLB and PD indicated, for the first time, the existence of different α-synuclein strains in these groups. Therefore, our study contributes to a better understanding of the clinical heterogeneity among α-synucleinopathies, offers an opportunity for a specific diagnosis, and opens new avenues for the future development of strain-specific therapies. Ann Neurol 2019;85:691-703.
000140668 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000140668 542__ $$2Crossref$$i2019-03-27$$uhttp://onlinelibrary.wiley.com/termsAndConditions#vor
000140668 542__ $$2Crossref$$i2019-03-27$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1
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000140668 650_2 $$2MeSH$$aAged
000140668 650_2 $$2MeSH$$aAged, 80 and over
000140668 650_2 $$2MeSH$$aBrain: metabolism
000140668 650_2 $$2MeSH$$aBrain: pathology
000140668 650_2 $$2MeSH$$aBrain Chemistry: physiology
000140668 650_2 $$2MeSH$$aFemale
000140668 650_2 $$2MeSH$$aHumans
000140668 650_2 $$2MeSH$$aMale
000140668 650_2 $$2MeSH$$aProtein Isoforms: analysis
000140668 650_2 $$2MeSH$$aProtein Isoforms: metabolism
000140668 650_2 $$2MeSH$$aSpectrum Analysis, Raman: methods
000140668 650_2 $$2MeSH$$aSynucleinopathies: metabolism
000140668 650_2 $$2MeSH$$aSynucleinopathies: pathology
000140668 650_2 $$2MeSH$$aalpha-Synuclein: analysis
000140668 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000140668 7001_ $$0P:(DE-2719)9000287$$aSchmitz, Matthias$$b1$$eCorresponding author$$udzne
000140668 7001_ $$0P:(DE-HGF)0$$aLlorens, Franc$$b2
000140668 7001_ $$0P:(DE-2719)9000327$$aVillar-Piqué, Anna$$b3$$udzne
000140668 7001_ $$0P:(DE-2719)2810657$$aCramm, Maria$$b4$$udzne
000140668 7001_ $$0P:(DE-2719)9000851$$aThom, Tobias$$b5$$udzne
000140668 7001_ $$0P:(DE-2719)9000766$$aSilva-Correia, Susana$$b6$$udzne
000140668 7001_ $$ada Cunha, José Eriton Gomes$$b7
000140668 7001_ $$aMöbius, Wiebke$$b8
000140668 7001_ $$0P:(DE-HGF)0$$aOuteiro, Tiago F$$b9
000140668 7001_ $$aÁlvarez, Valentina González$$b10
000140668 7001_ $$aBanchelli, Martina$$b11
000140668 7001_ $$aD'Andrea, Cristiano$$b12
000140668 7001_ $$ade Angelis, Marella$$b13
000140668 7001_ $$0P:(DE-2719)9000358$$aZafar, Saima$$b14$$udzne
000140668 7001_ $$aRabano, Alberto$$b15
000140668 7001_ $$aMatteini, Paolo$$b16
000140668 7001_ $$0P:(DE-2719)2000058$$aZerr, Inga$$b17$$eLast author$$udzne
000140668 77318 $$2Crossref$$3journal-article$$a10.1002/ana.25446$$b : Wiley, 2019-03-27$$n5$$p691-703$$tAnnals of Neurology$$v85$$x0364-5134$$y2019
000140668 773__ $$0PERI:(DE-600)2037912-2$$a10.1002/ana.25446$$gVol. 85, no. 5, p. 691 - 703$$n5$$p691-703$$q85:5<691 - 703$$tAnnals of neurology$$v85$$x0364-5134$$y2019
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