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Recent AD work related in vivo LC magnetic resonance imaging (MRI) integrity to tau and cognitive decline; however, relationships of LC integrity to age, tau, and cognition in autosomal dominant AD (ADAD) remain unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We associated LC integrity (3T\u2010MRI) with estimated years of onset, cortical amyloid beta, regional tau (positron emission tomography [PET]) and memory (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word\u2010List\u2010Learning) among 27 carriers and 27 non\u2010carriers of the presenilin\u20101 (<jats:italic>PSEN1<\/jats:italic>) <jats:italic>E280A<\/jats:italic> mutation. Longitudinal changes between LC integrity and tau were evaluated in 10 carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LC integrity started to decline at age 32 in carriers, 12 years before clinical onset, and 20 years earlier than in sporadic AD. LC integrity was negatively associated with cortical tau, independent of amyloid beta, and predicted precuneus tau increases. LC integrity was positively associated with memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings support LC integrity as marker of disease progression in preclinical ADAD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12656","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T09:19:16Z","timestamp":1647508756000},"page":"169-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Waning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer's disease"],"prefix":"10.1002","volume":"19","author":[{"given":"Heidi I.L.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"},{"name":"Faculty of Health, Medicine and Life Sciences School for Mental Health and Neuroscience Alzheimer Centre Limburg Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Alex","family":"Becker","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Kwong","sequence":"additional","affiliation":[{"name":"Athinoula A. 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Martinos Center for Biomedial Imaging Department of Radiology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Alzheimer Research and Treatment Department of Neurology Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Alzheimer Research and Treatment Department of Neurology Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts 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