{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:51:37Z","timestamp":1782409897251,"version":"3.54.5"},"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5U01NS055903"],"award-info":[{"award-number":["5U01NS055903"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Although adult Huntington\u2019s disease (HD) studies have significantly advanced our understanding of the course of degeneration, they may underrepresent critical neurodevelopmental aspects of the disease. Significant gaps remain in understanding how mutant huntingtin affects early neurodevelopment, its long-term impact, as well as potential implications for treatment outcomes. The Childhood to Adult Neurodevelopment in Gene-Expanded Huntington\u2019s Disease (\n                    <jats:italic>ChANGE-HD;<\/jats:italic>\n                    NCT01951588) study aims to evaluate brain structure and function in premanifest, at-risk children and young adults, and explore HD\u2019s developmental origins. Here, we introduce the ChANGE-HD study, which will investigate and integrate the neurodevelopmental and neurodegenerative aspects of HD. The ChANGE-HD study is a prospective, seven-year multi-site observational study with an accelerated longitudinal design, where participants are not bound to a fixed schedule across multiple visits. Four hundred and fifty participants aged 6\u201330 years who are at risk for HD will be recruited and asked to return for multiple visits (if possible). At each visit, cognitive, motor, behavioral, blood\/saliva, and MRI data are collected. Alongside ChANGE-HD, we are also recruiting individuals for the juvenile-onset HD (JOHD) study to investigate the neuropathology of this rarer form of HD. ChANGE-HD represents the first prospective multi-site study to systematically document brain structure and function during the premanifest phase of HD in children and young adults. Data collection is ongoing with first results anticipated in 2026\u20132027. The ChANGE-HD approach is likely to provide novel physiological insights and guide the development of therapeutic strategies tailored to both the developmental and degenerative phases of the disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0336088","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:45:02Z","timestamp":1782409502000},"page":"e0336088","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Childhood to Adult Neurodevelopment in Gene-Expanded Huntington\u2019s Disease (ChANGE-HD): A prospective longitudinal neurodevelopmental study of Huntington\u2019s disease"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5047-0166","authenticated-orcid":true,"given":"Mohit","family":"Neema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Halabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-8259","authenticated-orcid":true,"given":"Michael V.","family":"Freedberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy C.","family":"Nopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ChANGE-HD investigators, coordinators, and consultants","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"6","key":"pone.0336088.ref001","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"M Macdonald","year":"1993","journal-title":"Cell"},{"issue":"12","key":"pone.0336088.ref002","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nrn1806","article-title":"Normal huntingtin function: an alternative approach to Huntington\u2019s disease","volume":"6","author":"E Cattaneo","year":"2005","journal-title":"Nat Rev Neurosci"},{"issue":"2","key":"pone.0336088.ref003","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41418-021-00914-9","article-title":"The evolutionary history of the polyQ tract in huntingtin sheds light on its functional pro-neural activities","volume":"29","author":"R Iennaco","year":"2022","journal-title":"Cell Death Differ"},{"issue":"53","key":"pone.0336088.ref004","first-page":"314","article-title":"TRPing up the genome: Tandem repeat polymorphisms as dynamic sources of genetic variability in health and disease","volume":"10","author":"AJ Hannan","year":"2010","journal-title":"Discov Med"},{"issue":"2","key":"pone.0336088.ref005","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/07391102.2012.677771","article-title":"Origin and evolution of genes and genomes. 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