Abnormalities of peptide metabolism in Alzheimer disease

Curr Neurovasc Res. 2004 Oct;1(4):317-23. doi: 10.2174/1567202043362117.


The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / classification
  • Aspartic Acid Endopeptidases / metabolism
  • Endopeptidases
  • Endothelin-1 / pharmacology
  • Humans
  • Models, Biological
  • Peptide Hydrolases / metabolism
  • Peptides / metabolism*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Endothelin-1
  • Peptides
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Peptide Hydrolases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human