Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein

Ann N Y Acad Sci. 2000;924:17-25. 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 beta-protein (A beta). Mounting evidence from many laboratories supports an A beta accumulation in limbic and association cortices as the fundamental initiator of the disease, with attendant therapeutic implications.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Brain / metabolism
  • Brain / pathology
  • Cytotoxins / metabolism
  • Humans
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology


  • Amyloid beta-Peptides
  • Cytotoxins