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Brain arteriolosclerosis

Lookup NU author(s): Professor Raj KalariaORCiD


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© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer’s disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Publication metadata

Author(s): Blevins BL, Vinters HV, Love S, Wilcock DM, Grinberg LT, Schneider JA, Kalaria RN, Katsumata Y, Gold BT, Wang DJJ, Ma SJ, Shade LMP, Fardo DW, Hartz AMS, Jicha GA, Nelson KB, Magaki SD, Schmitt FA, Teylan MA, Ighodaro ET, Phe P, Abner EL, Cykowski MD, Van Eldik LJ, Nelson PT

Publication type: Review

Publication status: Published

Journal: Acta Neuropathologica

Year: 2021

Volume: 141

Issue: 1

Pages: 1-24

Print publication date: 01/01/2021

Online publication date: 24/10/2020

Acceptance date: 05/10/2020

ISSN (print): 0001-6322

ISSN (electronic): 1432-0533

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s00401-020-02235-6

PubMed id: 33098484