In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues.
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.
Kingston
I B
IB
Department of Pathology, University of Cambridge, UK.
Castro
M J
MJ
Anderson
S
S
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); C075222:amyloid beta-protein (1-42); D005340:Fibrinogen; D010959:Tissue Plasminogen Activator