Proteolytic processing of Alzheimer's disease βA4 amyloid precursor protein in human platelets

Abstract

The processing of amyloid precursor protein (APP) and production of βA4 amyloid are events likely to influence the development and progression of Alzheimer's disease, since βA4 is the major constituent of amyloid deposited in this disorder. Our previous studies showed that human platelets contain full-length APP (APP(FL)) and are a suitable substrate to study normal APP processing. In the present study, we show that a 22-kDa βA4-containing carboxyl-terminal fragment (22-CTF) of APP is present in unstimulated platelets. Both APP(FL) and 22-CTF are proteolytically degraded when platelets are activated with thrombin, collagen, or calcium ionophore A23187. Complete cleavage of APP(FL) and 22-CTF..