PLATELETS ARE THE PRIMARY SOURCE OF AMYLOID BETA-PEPTIDE IN HUMAN BLOOD

The main component of Alzheimer's disease (AD) amyloid deposits is amy loid beta-peptide (A beta), a fragment of the larger amyloid precursor protein (APP). The cellular source of A beta is not known, but a circ ulatory origin has been postulated. We studied human blood from health y individuals and found that platelets account for almost 90% of the t otal anti-A beta immunoreactivity detected in whole blood. Using rever se-phase HPLC, we identified a platelet peptide which corresponds to A beta by three criteria. (a) it shares a retention time with the synth etic A beta(1-40) peptide in two consecutive HPLC tests; (b) it intera cts with two anti-A beta antibodies in separate ELISAs; and, (c) its p artial N-terminal amino acid sequence closely matches that of A beta. The detection of this peptide in platelets indicates that, aside from the well-known non-amyloidogenic (secretory) pathway, the processing o f APP in platelets from healthy individuals also involves an amyloidog enic pathway. These findings are consistent with the view that platele ts are one of the major sources of A beta in the circulation. (C) 1995 Academic Press, Inc.