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

• Published in: Annals of the New York Academy of Sciences Vol. 924; no. 1; pp. 17 - 25
• Main Author: SELKOE, DENNIS J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2000
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid β-protein; Brain - metabolism; Brain - pathology; Cytotoxins - metabolism; Dementia; Humans; Neurofibrillary tangles; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Presenilins; Senile plaques
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2000.tb05554.x

: 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.