@article{212bb429feee4b1093e7660d47a0a947,
title = "Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy",
abstract = "INTRODUCTIONWe investigated the link between locus coeruleus (LC) pathology and cerebral microangiopathy in two large neuropathology datasets. METHODSWe included data from the National Alzheimer's Coordinating Center (NACC) database (n = 2197) and Religious Orders Study and Rush Memory and Aging Project (ROSMAP; n = 1637). 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, ante mortem cognitive status, and presence of vascular and genetic risk factors. RESULTSLC hypopigmentation was associated with higher odds of overall CAA in the NACC dataset, leptomeningeal CAA in the ROSMAP dataset, and arteriolosclerosis in both datasets. DISCUSSIONLC 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-norepinephrine system on cerebrovascular health are warranted. HighlightsWe associated locus coeruleus (LC) pathology and cerebral microangiopathy in two large autopsy datasets.LC hypopigmentation was consistently related to arteriolosclerosis in both datasets.LC hypopigmentation was related to cerebral amyloid angiopathy (CAA) presence in the National Alzheimer's Coordinating Center dataset.LC hypopigmentation was related to leptomeningeal CAA in the Religious Orders Study and Rush Memory and Aging Project dataset.LC degeneration may play a role in the pathways relating vascular pathology to Alzheimer's disease.",
keywords = "Alzheimer's disease, arteriolosclerosis, autopsy, cerebral amyloid angiopathy, locus coeruleus, BLOOD-BRAIN-BARRIER, MILD COGNITIVE IMPAIRMENT, SMALL VESSEL DISEASE, NEUROPATHOLOGIC ASSESSMENT, HYPERPHOSPHORYLATED TAU, AMYLOID ANGIOPATHY, OLDER PERSONS, RUSH MEMORY, CERULEUS, NORADRENALINE",
author = "W.M. Freeze and {Van Veluw}, S.J. and W.J. Jansen and D.A. Bennett and H.I.L. Jacobs",
note = "Funding Information: The authors are very thankful to all participants in the NACC and ROSMAP studies, and to those contributing to the data collections. This work was supported by Alzheimer Nederland grant WE.03‐2018‐13 (PI Whitney Freeze), the National Institutes of Health (R01AG062559, R01AG068062, R21AG074220 [PI Heidi Jacobs, PhD]) and the Alzheimer's Association (AARG‐22‐920434 [PI Heidi Jacobs, PhD]). The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA‐funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). The ROSMAP study is funded by NIH grant P30AG10161, R01AG15819, and R01AG17917 (PI David Bennett, MD). Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2023",
month = nov,
doi = "10.1002/alz.13096",
language = "English",
volume = "19",
pages = "5023--5035",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons Inc.",
number = "11",
}