BETA-AMYLOID AUGMENTS PLATELET-AGGREGATION - REDUCED ACTIVITY OF FAMILIAL ANGIOPATHY-ASSOCIATED MUTANTS

The beta-amyloid (A beta) peptide is present both in serum and in plat elets, however it is unclear whether A beta plays a role in platelet f unction. We have now investigated the effects of soluble A beta on pla telet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of f ocal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine dipho sphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios . The structure activity requirements for A beta activity showed intri guing constraints. Only full length A beta has significant activity. T runcated A beta peptides, such as A beta(1-16) or A beta(25-35), or re verse A beta(40-1) all show little or no activity. We also examined th e activity of mutant A beta peptides, corresponding with the APP(692A- ->G) and APP(693E-->Q) (at A beta 21 and A beta 22, respectively) whic h are found in familiar Alzheimer's disease and hereditary cerebral he morrhagic amyloidosis, Dutch type (HCHWA-D), and found that these pept ides showed little or no activity. These results suggest that A beta i nteracts with platelets in a highly specific manner and may play a rol e in regulating platelet function.