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Genetic association studies link variation in <jats:italic>LRRK2<\/jats:italic> to idiopathic Parkinson disease (iPD) risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Through measurements of the LRRK2 kinase substrate pT73\u2010Rab10 in urinary extracellular vesicles, this study seeks to understand how LRRK2 kinase activity might change with iPD progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an immunoblotting approach validated in LRRK2 transgenic mice, the ratio of pT73\u2010Rab10 to total Rab10 protein was measured in extracellular vesicles from a cross\u2010section of G2019S <jats:italic>LRRK2<\/jats:italic> mutation carriers (N\u00a0=\u00a045 participants) as well as 485 urine samples from a novel longitudinal cohort of iPD and controls (N\u00a0=\u00a085 participants). Generalized estimating equations were used to conduct analyses with commonly used clinical scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although the G2019S <jats:italic>LRRK2<\/jats:italic> mutation did not increase pT73\u2010Rab10 levels, the ratio of pT73\u2010Rab10 to total Rab10 nominally increased over baseline in iPD urine vesicle samples with time, but did not increase in age\u2010matched controls (1.34\u2010fold vs. 1.05\u2010fold, 95% confidence interval [CI], 0.004\u20130.56; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.046; Welch's <jats:italic>t<\/jats:italic> test). Effect estimates adjusting for sex, age, disease duration, diagnosis, and baseline clinical scores identified increasing total Movement Disorder Society\u2010Sponsored Revision of the Unified (MDS\u2010UPDRS) scores (\u03b2\u00a0=\u00a00.77; CI, 0.52\u20131.01; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0001) with each fold increase of pT73\u2010Rab10 to total Rab10. Lower Montreal Cognitive Assessment (MoCA) score in iPD is also associated with increased pT73\u2010Rab10.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results provide initial insights into peripheral LRRK2\u2010dependent Rab phosphorylation, measured in biobanked urine, where higher levels of pT73\u2010Rab10 are associated with worse disease progression. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29043","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T07:49:54Z","timestamp":1651823394000},"page":"1454-1464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Shijie","family":"Wang","sequence":"first","affiliation":[{"name":"Duke Center for Neurodegeneration and Neurotherapeutics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakthi","family":"Unnithan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Bryant","sequence":"additional","affiliation":[{"name":"Duke Center for Neurodegeneration and Neurotherapeutics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Chang","sequence":"additional","affiliation":[{"name":"Duke Center for Neurodegeneration and Neurotherapeutics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana S.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6427-7485","authenticated-orcid":false,"given":"Alexander","family":"Pantelyat","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-0893","authenticated-orcid":false,"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University  Baltimore Maryland USA"},{"name":"Neurodegeneration and Stem Cell Programs, Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Solomon H. 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