Inflammation, antichymotrypsin, and lipid metabolism: autogenic etiology of Alzheimer's disease

Bioessays. 1998 Dec;20(12):1039-46. doi: 10.1002/(SICI)1521-1878(199812)20:12<1039::AID-BIES10>3.0.CO;2-Z.

Abstract

Alzheimer's disease is a multifactor pathology, some of whose causes have been inferred from genetic studies, primarily of associated early-onset cases. Much evidence implicates the A beta amyloid peptide as a neurotoxic agent, with chronic inflammation as an accompanying physiological contributor to the disease. The two central questions of how A beta kills neurons and of the autogenic basis of disease remain unanswered. We hypothesize that specific interactions of A beta with the inflammatory serpin, alpha 1-antichymotrypsin, abolish the serpin proteinase inhibitor activity and stimulate formation of the neurotoxic fibrillar form of A beta. Further, the fibrillar A beta interacts with specific cell surface receptors, prompting its own biosynthesis and disrupting cellular cholesterol metabolism. These molecular and cellular interactions autogenically sustain the processes of A beta formation, fibrillization, and receptor interaction, the last of which culminates in neuronal death through disruption of cholesterol metabolism.

Publication types

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

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Inflammation*
  • Lipid Metabolism*
  • alpha 1-Antichymotrypsin / metabolism*

Substances

  • Amyloid beta-Peptides
  • alpha 1-Antichymotrypsin