SECRETION OF ALZHEIMERS-DISEASE A-BETA AMYLOID PEPTIDE BY ACTIVATED HUMAN PLATELETS

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.