Alzheimer's disease (AD) is characterized by the deposition of A beta
(beta A4) peptides of 39 to 43 amino acid residues, which are normal c
ellular metabolic products derived by proteolysis of the amyloid precu
rsor protein (APP). The physiologic function of A beta/APP in vivo is
poorly understood. We analyzed human platelets for A beta production b
y immunoprecipitation coupled to immunoblotting. A 4-kd A beta fragmen
t that comigrates with an A beta 40 synthetic peptide and reacts with
several antibodies specific for the N- and C-termini of A beta is dete
cted. The majority of platelet A beta appears to end at residue 40, as
determined by immunoreactivity with an A beta 40-specific antibody. F
urthermore, A beta is secreted upon platelet stimulation with the phys
iologic agonists thrombin and collagen, together with secretion of sol
uble APP (sAPP). A comparison between serum and plasma shows a 1.6-fol
d increase in A beta levels and a 2.4-fold increase in sAPP levels in
serum. This is consistent with the view that platelets are the primary
source of circulating A beta and APP. The release of platelet A beta
by physiologic stimuli suggests that it may play a role in platelet ag
gregation and coagulation or in the repair mechanisms associated with
injury.