A beta, aging, and Alzheimer's disease: a tale, models, and hypotheses.
In this paper we explore the potential functional role of the A beta peptides in the context of Alzheimer's disease (AD). We begin by defining the morphology of the amyloid deposits in relation to surrounding glial cells and, more importantly, in relation to the brain vasculature. Amyloid accumulation in the brain's microvasculature causes disturbances in the blood-brain barrier (BBB), and in larger arteries, impairment in control of regional cerebral blood flow due to myocyte degeneration. We postulate that the deposition of vascular amyloid may represent a hydrophobic protein plaster to seal leaks in the BBB, occasionally observed in aging and catastrophically common in AD. The vasoconstrictive activity of A beta may also be related to leaky vessels whereby decreasing the arterial diameter may also help to control breaches in the BBB. The admission of plasma neurotoxic proteins into the brain may be controlled by activation of microglia elicited by soluble A beta peptides creating a subtle, but permanent brain inflammatory reaction. We also delve into the influence that cholesterol metabolism may have in membrane topology and A beta production, and the close correlations that exist between cardiovascular disease and AD. Finally, we speculate about the possibility of a peripheral source of A beta that may, by crossing the BBB, contribute to the vascular and parenchymal deposits of A beta in the AD brain.
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D004660:Encephalitis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D016229:Amyloid beta-Peptides