Oxidative Stress and Cell Membranes in the Pathogenesis of Alzheimer's Disease

Abstract

Amyloid β proteins and oxidative stress are believed to have central roles in the development of Alzheimer's disease. Lipid membranes are among the most vulnerable cellular components to oxidative stress, and membranes in susceptible regions of the brain are compositionally distinct from those in other tissues. This review considers the evidence that membranes are either a source of neurotoxic lipid oxidation products or the target of pathogenic processes involving amyloid β proteins that cause permeability changes or ion channel formation. Progress toward a comprehensive theory of Alzheimer's disease pathogenesis is discussed in which lipid membranes assume both roles and promote the conversion of monomeric amyloid β proteins into fibrils, the pathognomonic histopathological lesion of the disease.