Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy

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.