Aging and cerebrovascular dysfunction: contribution of hypertension, cerebral amyloid angiopathy, and immunotherapy.
Age-related cerebrovascular dysfunction contributes to ischemic stroke, intracerebral hemorrhages (ICHs), microbleeds, cerebral amyloid angiopathy (CAA), and cognitive decline. Importantly, there is increasing recognition that this dysfunction plays a critical secondary role in many neurodegenerative diseases, including Alzheimer's disease (AD). Atherosclerosis, hypertension, and CAA are the most common causes of blood-brain barrier (BBB) lesions. The accumulation of amyloid beta (Aβ) in the cerebrovascular system is a significant risk factor for ICH and has been linked to endothelial transport failure and blockage of perivascular drainage. Moreover, recent anti-Aβ immunotherapy clinical trials demonstrated efficient clearance of parenchymal amyloid deposits but have been plagued by CAA-associated adverse events. Although management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA. Thus, there is a critical need for new strategies that improve BBB function and limit the development of β-amyloidosis in the cerebral vasculature.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
Vitaly
V
Vasilevko
Giselle F
GF
Passos
Daniel
D
Quiring
Elizabeth
E
Head
Richard C
RC
Kim
Mark
M
Fisher
David H
DH
Cribbs
D000375:Aging / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000276:immunology; D000818:Animals; D001812:Blood-Brain Barrier; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology* / Q000628:therapy; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000628:therapy; D007167:Immunotherapy; D002537:Intracranial Arteriosclerosis / Q000209:etiology / Q000628:therapy
D016229:Amyloid beta-Peptides