@article{ef1da1af39cd43c3bb27ec02f3f1fbf5,
title = "Urine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3",
abstract = "Introduction: Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients. Methods: We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay. Results: PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset. Conclusion: As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3.",
keywords = "Ataxin-3 (ATXN3), Biomarker, Polyglutamine (PolyQ), Spinocerebellar ataxia type 3 (SCA3)/machado-josephs disease (MJD), Urine",
author = "Yuka Koike and Jansen-West, {Karen R.} and {Hanna AL-Shaikh}, Rana and Yari Carlomagno and Yuping Song and Dunmore, {Judith A.} and LeDoux, {Mark S.} and Friedman, {Joseph H.} and Pena, {Ashley B.} and Uitti, {Ryan J.} and Jacek Zaremba and {van Gerpen}, {Jay A.} and Pfeiffer, {Ronald F.} and Venka Veerappan and Ikuko Aiba and Rina Hashimoto and Giles, {Samuel S.} and Shah, {Jaimin S.} and Tipton, {Philip W.} and Huang, {Josephine F.} and Wierenga, {Klaas J.} and Jan Aasly and Fryer, {John D.} and Leonard Petrucelli and Wszolek, {Zbigniew K.} and Mercedes Prudencio",
note = "Funding Information: This work was supported by the National Institutes of Health/National Institute of Neurological Disorder and Stroke [RF1NS120992-01 (M.P.); R35NS097273 (L.P.); P01NS084974 (L.P.); P01NS099114 (L.P.); R01NS088689 (L.P.); R21NS084528 (L.P.)]; National Institute of Environmental Health Sciences [R01ES20395 (L.P.)]; Department of Defense [ALSRP AL130125 (L.P.)]; Mayo Clinic Foundation (L.P.); Amyotrophic Lateral Sclerosis Association (L.P., M.P); Robert Packard Center for ALS Research at Johns Hopkins (L.P.); Target ALS Foundation (L.P.); Mayo Clinic Center for Regenerative Medicine (Z.K.W.); Mayo Clinic Neuroscience Focused Research Team (Z.K.W); gifts from The Sol Goldman Charitable Trust (Z.K.W.) and the Donald G. and Jodi P. Heeringa Family (Z.K.W., L.P.); the Haworth Family Professorship in Neurodegenerative Diseases fund (Z.K.W.); The Albertson Parkinson's Research Foundation (Z.K.W.). Funding Information: This work was supported by the National Institutes of Health /National Institute of Neurological Disorder and Stroke [ RF1NS120992-01 (M.P.); R35NS097273 (L.P.); P01NS084974 (L.P.); P01NS099114 (L.P.); R01NS088689 (L.P.); R21NS084528 (L.P.)]; National Institute of Environmental Health Sciences [ R01ES20395 (L.P.)]; Department of Defense [ ALSRP AL130125 (L.P.)]; Mayo Clinic Foundation (L.P.); Amyotrophic Lateral Sclerosis Association (L.P., M.P); Robert Packard Center for ALS Research at Johns Hopkins (L.P.); Target ALS Foundation (L.P.); Mayo Clinic Center for Regenerative Medicine (Z.K.W.); Mayo Clinic Neuroscience Focused Research Team (Z.K.W); gifts from The Sol Goldman Charitable Trust (Z.K.W.) and the Donald G. and Jodi P. Heeringa Family (Z.K.W., L.P.); the Haworth Family Professorship in Neurodegenerative Diseases fund (Z.K.W.); The Albertson Parkinson's Research Foundation (Z.K.W.). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = aug,
doi = "10.1016/j.parkreldis.2021.07.018",
language = "English (US)",
volume = "89",
pages = "151--154",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
}