Products of the Alzheimer's disease amyloid precursor protein generated by,β-secretase are present in human platelets, and secreted upon degranulation

Abstract

Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by /3-secretase generates the Nterminus ofA/3 (which deposits in the brain) and releases a secreted ectodomain of APP (sAPP/3). We identified in human platelets a band at 125 kDa corresponding to APP ectodomain ending with C-terminal methionine residue (APP671) as characterized by an antibody specificfor the C-terminal methionine residue of sAPP/3. The same antibody also detected bands at -105 and U125 kDa in human brain homogenates. Platelet sAPP/3 is an isoform containing the Kunitzprotease inhibitor domain (sAPP/3-KPI+) and is released into the medium when platelets are induced to aggregate using agonists such a..