Platelets Are the Primary Source of Amyloid β-Peptide in Human Blood

The main component of Alzheimer′s disease (AD) amyloid deposits is amyloid β-peptide (Aβ), a fragment of the larger amyloid precursor protein (APP). The cellular source of Aβ is not known, but a circulatory origin has been postulated. We studied human blood from healthy individuals and found that platelets account for almost 90% of the total anti-Aβ immunoreactivity detected in whole blood. Using reverse-phase HPLC, we identified a platelet peptide which corresponds to Aβ by three criteria. (a) it shares a retention time with the synthetic Aβ1-40 peptide in two consecutive HPLC tests; (b) it interacts with two anti-Aβ antibodies in separate ELISAs; and, (c) its partial N-terminal amino acid sequence closely matches that of Aβ. The detection of this peptide in platelets indicates that, aside from the well-known non-amyloidogenic (secretory) pathway, the processing of APP in platelets from healthy individuals also involves an amyloidogenic pathway. These findings are consistent with the view that platelets are one of the major sources of Aβ in the circulation.