Toward a Comprehensive Theory for Alzheimer's Disease. Hypothesis: Alzheimer's Disease Is Caused by the Cerebral Accumulation and Cytotoxicity of Amyloid β-Protein

Abstract

Abstract: A central challenge of research on Alzheimer's disease (AD) is to assemble the enormous body of scientific observations about the disorder, some of them seemingly in conflict with others, into a coherent and credible mechanism of pathogenesis. In this article, I attempt to synthesize the disparate findings on AD into a unified sequence that essentially begins with alterations in the production or clearance of the amyloid β-protein (Aβ). Mounting evidence from many laboratories supports an Aβ accumulation in limbic and association cortices as the fundamental initiator of the disease, with attendant therapeutic implications.