Platelet alpha- and beta-secretase activities: A preliminary study in normal human subjects

beta-amyloid (Abeta) arises from an amyloid precursor protein (APP) via beta- and gamma-secretase proteolysis. Platelets are the primary depot of APP in the circulation and may be a source of cerebral Abeta. We measured the platelet activities of alpha- and beta-secretases in normal individuals. Platelet alpha- and beta-secretase activities were linear with respect to incubation time and quantity of platelet extract included in the assays. beta-secretase activity, calculated relative to platelet count (PC) and platelet protein (PP), varied between individuals 3.5-fold and 4.6-fold, respectively. Meanwhile, alpha-secretase varied 3.75-fold and 5.8-fold. beta-secretase/alpha-secretase ratios varied 4.1-fold (PC) or 10.5-fold (PP). beta-secretase correlated with age (r = 0.779, p < 0.02, PP) and mean platelet volume (MPV) (r = 0.702, p < 0.05, PC). alpha-secretase correlated negatively with high-density lipoprotein (HDL) (-0.76, p < 0.01, PP). beta-secretase/alpha-secretase ratios correlated with MPV (r = 0.67, p < 0.05, PC) and HDL (r = 0.77, p < 0.02, PP). These data could indicate that platelet secretase activity is related to aging, platelet size and plasma lipoprotein levels. Clearly, however, this is a preliminary study involving a limited number of individuals and further, more detailed, investigations are required to establish that such relationships are valid.