Emerging insights from the genetics of cerebral small‐vessel disease

• Published in: Annals of the New York Academy of Sciences Vol. 1471; no. 1; pp. 5 - 17
• Main Authors: Rutten‐Jacobs, Loes C.A., Rost, Natalia S.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-07-2020
• Subjects: Brain; Brain - blood supply; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Cerebral Small Vessel Diseases - drug therapy; Cerebral Small Vessel Diseases - genetics; Cerebral Small Vessel Diseases - pathology; cerebral small‐vessel disease; Cerebrovascular Circulation - genetics; Cognitive ability; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Dementia disorders; Disease; Genetics; Humans; Microcirculation - genetics; Molecular modelling; Molecular structure; Neuroimaging; neurovascular unit; Parenchyma; stroke; Stroke - diagnostic imaging; Stroke - genetics; Stroke - pathology; Structure-function relationships; Vascular dementia; genetics; stroke; cerebral small-vessel disease; neurovascular unit
• ISSN: 0077-8923; 1749-6632; 1749-6632
• DOI: 10.1111/nyas.13998

Cerebral small‐vessel disease (cSVD) is a common cause of stroke, functional decline, vascular cognitive impairment, and dementia. Pathological processes in the brain's microcirculation are tightly interwoven with pathology in the brain parenchyma, and this interaction has been conceptualized as the neurovascular unit (NVU). Despite intensive research efforts to decipher the NVU's structure and function to date, molecular mechanisms underlying cSVD remain poorly understood, which hampers the development of cSVD‐specific therapies. Important steps forward in understanding the disease mechanisms underlying cSVD have been made using genetic approaches in studies of both monogenic and sporadic SVD. We provide an overview of the NVU's structure and function, the implications for cSVD, and the underlying molecular mechanisms of dysfunction that have emerged from recent genetic studies of both monogenic and sporadic diseases of the small cerebral vasculature.
A common cause of stroke is cerebral small‐vessel disease (cSVD), which results from pathological processes in the neurovascular unit (NVU). The review provides an overview of the structure and function of the NVU, the implications for cSVD, and the underlying molecular mechanisms of NVU dysfunction in cSVD that have emerged from recent genetic studies.