{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:58:39Z","timestamp":1787320719134,"version":"build-2736575974"},"reference-count":28,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JHD"],"published-print":{"date-parts":[[2024,3,29]]},"abstract":"<jats:p>Background: Huntington\u2019s disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown. Objective: To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD. Methods: We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls. Results: Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine. Conclusions: Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism.<\/jats:p>","DOI":"10.3233\/jhd-231511","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T11:47:46Z","timestamp":1709639266000},"page":"103-111","source":"Crossref","is-referenced-by-count":9,"title":["Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington\u2019s Disease"],"prefix":"10.1177","volume":"13","author":[{"given":"Anna C.","family":"Pfalzer","sequence":"first","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Shiino","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona G.","family":"Codreanu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy D.","family":"Sherrod","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Claassen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/JHD-231511_ref1","first-page":"971","article-title":"The Huntington\u2019s Disease Collaborative Research Group","volume":"72","author":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromo somes","year":"1993","journal-title":"Cell"},{"issue":"1","key":"10.3233\/JHD-231511_ref2","doi-asserted-by":"crossref","first-page":"a000588","DOI":"10.1101\/mcs.a000588","article-title":"Metabolomics: An emerging but powerful tool for precision medicine","volume":"1","author":"Clish","year":"2015","journal-title":"Cold Spring Harb Mol Case 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