{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T19:48:17Z","timestamp":1782416897006,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG051412"],"award-info":[{"award-number":["U01AG051412"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AG068054"],"award-info":[{"award-number":["U19AG068054"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS106384"],"award-info":[{"award-number":["NS106384"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Both micro\u2010 and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross\u2010sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Thirty cognitively stable (CS) adults with DS underwent diffusion\u2010weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The onset of such WM changes in DS has not yet been widely studied.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>WM microstructural properties correlated with plasma neurofilament light chain (NfL).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70023","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T05:55:15Z","timestamp":1732254915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-7511","authenticated-orcid":false,"given":"Herminia Diana","family":"Rosas","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel David","family":"Mercaldo","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Hasimoglu","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Family Medicine University of North Texas Health Science Center  Fort Worth Texas USA"},{"name":"Institute for Translational Research University of North Texas Health Science Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia R.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Powell","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging and Spectroscopy Center University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Dhungana","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Keater","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Yassa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's disease and the Aging Brain Department of Neurology Vagelos College of Physicians and Surgeons, Columbia University  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sid","family":"O'Bryant","sequence":"additional","affiliation":[{"name":"Department of Family Medicine University of North Texas Health Science Center  Fort Worth Texas USA"},{"name":"Institute for Translational Research University of North Texas Health Science Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20735"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7750(08)00004-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520440031017"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20163"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-j0001.2001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12040"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-018-2102-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.06.023"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09398-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30689-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00593-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12057"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201167"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0236384"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000926"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.1997.tb00692.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2788.2000.00264.x"},{"key":"e_1_2_7_19_1","article-title":"Plasma total\u2010tau and Neurofilament light chain (Nf\u2010L) as diagnostic biomarkers of Alzheimer's disease dementia and mild cognitive impairment in adults with Down syndrome","author":"Petersen ME","year":"2020","journal-title":"Journal of Alzheimer's Disease"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00336-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.051"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116131"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.06.021"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080713"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.05.027"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/2197-7364-1-S1-A29"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00587-5"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.053"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm102"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy229"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.11.027"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.042"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.137"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617718000206"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12080"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38520"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61799-1"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S319817"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12013"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.117728"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100087"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06120-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0515-3"}],"container-title":["Alzheimer's &amp; Dementia: Diagnosis, Assessment &amp; Disease Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dad2.70023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T18:45:42Z","timestamp":1760381142000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/dad2.70023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/dad2.70023"],"URL":"https:\/\/doi.org\/10.1002\/dad2.70023","archive":["Portico"],"relation":{},"ISSN":["2352-8729","2352-8729"],"issn-type":[{"value":"2352-8729","type":"print"},{"value":"2352-8729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70023"}}