Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain.
Cerebral amyloid angiopathy (CAA) is a feature of ageing and Alzheimer's disease (AD); it is also associated with intracerebral hemorrhage and stroke. Here, the pathogenesis of CAA and its effects on the brain are reviewed and the possible effects of CAA on therapies for Alzheimer's disease are evaluated. Tracer experiments in animals and observations on human brains suggest that peptides such as A beta are eliminated along the peri-arterial interstitial fluid drainage pathways that are effectively the lymphatics of the brain. In CAA, A beta becomes entrapped in drainage pathways in the walls of cerebral arteries, reflecting a failure of elimination of A beta from the ageing brain. One consequence of failure in clearance of A beta is accumulation of soluble and insoluble A beta associated with cognitive decline in AD. Replacement of vascular smooth muscle cells by A beta occurs in severe CAA with weakening of artery walls and increased risk of vessel rupture and intracerebral hemorrhage. Risk factors for CAA include mutations of the amyloid precursor protein (APP) gene and possession of the epsilon 4 allele of apolipoprotein E. There is also evidence that cerebrovascular disease may be a factor in the failure of elimination of A beta along perivascular pathways in sporadic AD; this would link ageing in cerebral arteries with the pathogenesis of Alzheimer's disease. If therapeutic agents, including anti-A beta antibodies, are to be used to eliminate A beta in the treatment of Alzheimer's disease, the effects of CAA on the treatment and the effects of the treatment on the CAA need to be considered.
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D016229:Amyloid beta-Peptides