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The role of beta amyloid in Alzheimer's disease: still a cause of everything or the only one who got caught?

Pharmacol Res. 2004 Oct;50(4):397-409. doi: 10.1016/j.phrs.2003.12.028.

Abstract

The beta amyloid (A beta) protein is a key molecule in the pathogenesis of Alzheimer's disease (AD). The tendency of the A beta peptide to aggregate, its reported neurotoxicity, and genetic linkage studies, have led to a hypothesis of AD pathogenesis that many AD researchers term the amyloid cascade hypothesis. In this hypothesis, an increased production of A beta results in neurodegeneration and ultimately dementia through a cascade of events. In the past 15 years, debate amongst AD researchers has arisen as to whether A beta is a cause or an effect of the pathogenic process. Recent in vitro and in vivo research has consolidated the theory that A beta is the primary cause, initiating secondary events, culminating in the neuropathological hallmarks associated with AD. This research has led to the development of therapeutic agents, currently in human clinical trials, which target A beta.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Alzheimer Vaccines / therapeutic use
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspartic Acid Endopeptidases
  • Chelation Therapy
  • Endopeptidases / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Hormones / therapeutic use
  • Humans
  • Mutation

Substances

  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Hormones
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human