In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues

Nat Med. 1995 Feb;1(2):138-42. doi: 10.1038/nm0295-138.

Abstract

We have studied the effects of amyloid beta-peptide analogues on the activity of tissue-type plasminogen activator (t-PA) in vitro. We have found that these peptides have a marked stimulatory effect upon plasminogen activation by t-PA, comparable to that of known stimulators of t-PA. This stimulatory activity appears to increase when beta-peptides form aggregated fibrillar structures similar to those found in amyloid deposits. This finding is significant in that it may provide insights into the pathogenesis of hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) and cerebral amyloid angiopathy-related cerebral haemorrhage. It may also provide an explanation for the deaths resulting from intracerebral haemorrhage that have occurred in patients undergoing t-PA treatment for acute myocardial infarction.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / pharmacology*
  • Fibrinogen / pharmacology
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Mutation
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Tissue Plasminogen Activator / metabolism*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-28)
  • amyloid beta-protein (1-42)
  • Fibrinogen
  • Tissue Plasminogen Activator