Brain arteriolosclerosis

Abstract

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 A a a b c-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 include consideration of comorbid diseases, B-ASC is independently associated with impairments in 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.

Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to Alzheimer’s and small vessel disease pathologies

“…Additionally, the total number of areas with CAA out of nine maximum was also determined (28,29). The SI score allows the quantification of arteriolosclerosis as a measure of SVD severity (33,34). The SI of each PARWM case used in this study was measured using COL4 immunostained scanned sections using the formula; SI = 1 − [Internal diameter (Dint)/External diameter (Dext)] (14).…”

Dysregulation of Systemic Immunity in Aging and Dementia

“…Most individuals with profound cognitive decline will have a high burden of neuropathological changes, including amyloid plaques and neurofibrillary tangles, vascular, synucleinopathy, and TDP-43 pathology ( Karanth et al, 2020 ). We also know that the vascular contribution to cognitive impairment and dementia (VCID) is profound, and here too, we can see the connection between the body and the brain ( Ighodaro et al, 2017 ; Blevins et al, 2020 ; Zlokovic et al, 2020 ).…”

Molecular Pathobiology of the Cerebrovasculature in Aging and in Alzheimers Disease Cases With Cerebral Amyloid Angiopathy

“…At autopsy, other vascular associated morphological lesions can be observed in aging and AD brains such as degeneration of arterioles and leptomeningeal vessels (Vinters et al, 1994;Kalaria, 1996;Farkas and Luiten, 2001), capillaries and mural cells (Miyakawa and Kuramoto, 1989;Hashimura et al, 1991;Kimura et al, 1991;Farkas et al, 2000;Østergaard et al, 2013); mitochondria abnormalities and deposition of phagolysosomes and lipofuscin in cerebrovascular cells (Miyakawa and Kuramoto, 1989); degeneration of the blood brain barrier (Deane and Zlokovic, 2007), arteriolar wall thickening or arteriolosclerosis (Neltner et al, 2014;Blevins et al, 2021), propensity for plaque build up in cerebral arteries (Roher et al, 2004;Beach et al, 2007;Yarchoan et al, 2012), immune cell recruitment and influx of blood borne proteins (Itagaki et al, 1988;Rogers et al, 1988;Togo et al, 2002;Grammas et al, 2006;Di Marco et al, 2015;Merlini et al, 2018).…”