Copper, β-amyloid, and Alzheimer's disease: Tapping a sensitive connection

摘要

Redox chemistry arising from transition metals copper and iron are the principal chemical origin of the radicals and reactive oxygen species that are implicated in the pathogenesis of a number of degenerative diseases, such as Alzheimer's disease (AD) and atherosclerosis. In health the brain strictly regulates the movement of these metals across the blood-brain barrier (BBB), which is relatively impermeable to fluctuations in blood levels. This barrier is relevant in AD because the disease is characterized by the accumulation in the brain of β-amyloid (Aβ), a copper/zinc-metal-loprotein that aggregates and becomes redox-active in the presence of excessive amounts of these metals. We are only beginning to unravel the age-dependent failure of metal homeostatic mechanisms of the brain that contribute to abnormal Aβ biochemistry in AD.