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We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock\u2010in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5\u00a0years before onset. Cross\u2010sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock\u2010in mice, here also starting already at the presymptomatic stage, closely following ataxin\u20103 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross\u2010species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity\u2010to\u2010onset and, potentially, treatment\u2010response markers in both human and preclinical SCA3 trials.<\/jats:p>","DOI":"10.15252\/emmm.201911803","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T09:07:39Z","timestamp":1591607259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and 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MR receives funding from the Polish National Center for Research and Development (grant IS\u20102\/230\/NCBR\/2015). TK receives\/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the German Federal Ministry of Education and Research (BMBF), the German Federal Ministry of Health (BMG), the Robert Bosch Foundation, the European Union (EU), and the National Institutes of Health (NIH). He has received consulting fees from Biohaven and UBC. He has received a speaker honorarium from Novartis. MS received speaker's honoraria and research support from Actelion Pharmaceuticals, unrelated to the current project and manuscript. The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMMM201911803"}}