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Generalized estimating equations and logistic regression were used to examine associations between LC hypopigmentation and presence of cerebral amyloid angiopathy (CAA) or arteriolosclerosis, correcting for age at death, sex, cortical Alzheimer's disease (AD) pathology, <jats:italic>ante mortem<\/jats:italic> cognitive status, and presence of vascular and genetic risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>LC hypopigmentation was associated with higher odds of overall CAA in the NACC dataset, leptomeningeal CAA in the ROSMAP dataset, and arteriolosclerosis in both datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>LC pathology is associated with cerebral microangiopathy, independent of cortical AD pathology. LC degeneration could potentially contribute to the pathways relating vascular pathology to AD. Future studies of the LC\u2013norepinephrine system on cerebrovascular health are warranted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We associated locus coeruleus (LC) pathology and cerebral microangiopathy in two large autopsy datasets.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LC hypopigmentation was consistently related to arteriolosclerosis in both datasets.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LC hypopigmentation was related to cerebral amyloid angiopathy (CAA) presence in the National Alzheimer's Coordinating Center dataset.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LC hypopigmentation was related to leptomeningeal CAA in the Religious Orders Study and Rush Memory and Aging Project dataset.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LC degeneration may play a role in the pathways relating vascular pathology to Alzheimer's disease.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13096","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T01:50:35Z","timestamp":1682387435000},"page":"5023-5035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy"],"prefix":"10.1002","volume":"19","author":[{"given":"Whitney Marilyn","family":"Freeze","sequence":"first","affiliation":[{"name":"Department of Radiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Psychiatry and Neuropsychology Alzheimer Center Limburg School for Mental Health and Neuroscience Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Janneke","family":"Van Veluw","sequence":"additional","affiliation":[{"name":"Department of Radiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Neurology J. Philip Kistler Stroke Research Center Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willemijn Josepha","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology Alzheimer Center Limburg School for Mental Health and Neuroscience Maastricht University  Maastricht the Netherlands"},{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Alan","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi Irma Louisa","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology Alzheimer Center Limburg School for Mental Health and Neuroscience Maastricht University  Maastricht the Netherlands"},{"name":"Gordon Center for Medical Imaging Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700003032"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201411"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2573"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c2937c"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0187-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.02.007"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12387"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0789-4"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.06.2362"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0411-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182897103"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj2511"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12257"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02248-1"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(03)00143-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2021.638007"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199708000-00008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.115"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3171\/2012.11.JNS12627"},{"key":"e_1_2_11_23_1","first-page":"309","article-title":"Mannitol derivate used as a marker for voltammetrically monitored transport across the blood\u2010brain barrier under condition of locus coeruleus stimulation","volume":"17","author":"Pavl\u00e1sek J","year":"1998","journal-title":"Gen Physiol Biophys"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00184295"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190090"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05223.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlab017"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11934"},{"key":"e_1_2_11_29_1","first-page":"158","article-title":"Vascular dysfunction\u2010The disregarded partner of Alzheimer's disease. 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