{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:39:49Z","timestamp":1773747589799,"version":"3.50.1"},"reference-count":86,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Collaborative","award":["200181\/Z\/15\/Z"],"award-info":[{"award-number":["200181\/Z\/15\/Z"]}]},{"name":"CHDI Foundation"},{"name":"Dementia Research Institute"},{"name":"UK"},{"name":"Medical Research Council"},{"DOI":"10.13039\/501100017506","name":"Alzheimer\u2019s Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100017506","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University College London Hospital\/University College London"},{"name":"Department of Health National Institute of Health Research Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Upregulation of functional network connectivity in the presence of structural degeneration is seen in the premanifest stages of Huntington\u2019s disease (preHD) 10\u201315 years from clinical diagnosis. However, whether widespread network connectivity changes are seen in gene carriers much further from onset has yet to be explored.<\/jats:p>\n               <jats:p>We characterized functional network connectivity throughout the brain and related it to a measure of disease pathology burden (CSF neurofilament light, NfL) and measures of structural connectivity in asymptomatic gene carriers, on average 24 years from onset. We related these measurements to estimates of cortical and subcortical gene expression.<\/jats:p>\n               <jats:p>We found no overall differences in functional (or structural) connectivity anywhere in the brain comparing control and preHD participants. However, increased functional connectivity, particularly between posterior cortical areas, correlated with increasing CSF NfL level in preHD participants. Using the Allen Human Brain Atlas and expression-weighted cell-type enrichment analysis, we demonstrated that this functional connectivity upregulation occurred in cortical regions associated with regional expression of genes specific to neuronal cells. This relationship was validated using single-nucleus RNAseq data from post-mortem Huntington\u2019s disease and control brains showing enrichment of neuronal-specific genes that are differentially expressed in Huntington\u2019s disease.<\/jats:p>\n               <jats:p>Functional brain networks in asymptomatic preHD gene carriers very far from disease onset show evidence of upregulated connectivity correlating with increased disease burden. These changes occur among brain areas that show regional expression of genes specific to neuronal GABAergic and glutamatergic cells.<\/jats:p>","DOI":"10.1093\/brain\/awac227","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T10:50:28Z","timestamp":1656327028000},"page":"3953-3967","source":"Crossref","is-referenced-by-count":8,"title":["Neurofilament light-associated connectivity in young-adult Huntington\u2019s disease is related to neuronal genes"],"prefix":"10.1093","volume":"145","author":[{"given":"Peter","family":"McColgan","sequence":"first","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Gregory","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-7169","authenticated-orcid":false,"given":"Paul","family":"Zeun","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-072X","authenticated-orcid":false,"given":"Angeliki","family":"Zarkali","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, University College London , London WC1N 3AR , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5271-0747","authenticated-orcid":false,"given":"Eileanoir 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Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-9439","authenticated-orcid":false,"given":"Akshay","family":"Nair","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"},{"name":"Max Planck University College London Centre for Computational Psychiatry and Ageing Research, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Estevez-Fraga","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Papoutsi","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-2140","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, University College London , London WC1N 3AR , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael I","family":"Scahill","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah 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