{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T19:03:05Z","timestamp":1779390185570,"version":"3.53.1"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lundbeck A\/S","award":["13737"],"award-info":[{"award-number":["13737"]}]},{"name":"Qatar Biomedical Research Institute under Start-up Fund","award":["SF 2017-0007"],"award-info":[{"award-number":["SF 2017-0007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aggregated \u03b1-synuclein (\u03b1Syn) protein is a core pathological feature of Parkinson\u2019s disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular \u03b1-synuclein (\u03b1Syn) species, including C-terminally truncated \u03b1Syn (C-\u03b1Syn), although it is unknown how C-\u03b1Syn species contribute to disease progression. Using recombinant C-\u03b1Syn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-\u03b1Syn may be involved in disease stratification. Comparing the seeding activity of aqueous-soluble fractions to detergent-soluble fractions, and using \u03b1Syn 1-130 as substrate for the RT-QuIC assay, the temporal cortex seeds differentiated PD and DLB from healthy controls. In contrast to the temporal cortex, where PD and DLB could not be distinguished, \u03b1Syn 1-130 seeded by the detergent-soluble fractions from the PD frontal cortex demonstrated greater seeding efficiency compared to the DLB frontal cortex. Moreover, proteinase K-resistant (PKres) fragments from the RT-QuIC end products using C-\u03b1Syn 1-130 or C-\u03b1Syn 1-115 were more obvious in the frontal cortex compared to the temporal cortex. Morphological examinations of RT-QuIC end products showed differences in the size of the fibrils between C-\u03b1Syn 1-130 and C-\u03b1Syn 1-115, in agreement with the RT-QuIC results. These data show that C-\u03b1Syn species can distinguish PD from DLB and suggest diversity in \u03b1Syn species across these synucleinopathies, which could play a role in disease progression.<\/jats:p>","DOI":"10.3390\/biom11060820","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T21:42:06Z","timestamp":1622497326000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["RT-QuIC Using C-Terminally Truncated \u03b1-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies"],"prefix":"10.3390","volume":"11","author":[{"given":"Ilaria","family":"Poggiolini","sequence":"first","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-5343","authenticated-orcid":false,"given":"Daniel","family":"Erskine","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant N.","family":"Vaikath","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janarthanan","family":"Ponraj","sequence":"additional","affiliation":[{"name":"Core Labs, Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Mansour","sequence":"additional","affiliation":[{"name":"Core Labs, Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Morris","sequence":"additional","affiliation":[{"name":"Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar M. A.","family":"El-Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/S1353-8020(13)70017-8","article-title":"alpha-Synucleinopathy phenotypes","volume":"20","author":"McCann","year":"2014","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with lewy bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. Natl. Acad. Sci. 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