β-Amyloid augments platelet aggregation: Reduced activity of familial angiopathy-associated mutants

The β-amyloid (Aβ) peptide is present both in serum and in platelets, however it is unclear whether Aβ plays a role in platelet function. We have now investigated the effects of soluble Aβ on platelet function and have found that low levels (0.1-1 nM) of soluble Aβ augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of Aβ to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:Aβ ratios. The structure activity requirements for Aβ activity showed intriguing constraints. Only full length Aβ has significant activity. Truncated Aβ peptides, such as Aβ_1-16 or Aβ_25-35, or reverse Aβ_40-1 all show little or no activity. We also examined the activity of mutant Aβ peptides, corresponding with the APP(692A→G) and APP(693→Q) (at Aβ21 and Aβ22, respectively) which are found in familial Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis. Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that Aβ interacts with platelets in a highly specific manner and may play a role in regulating platelet function.