Amyloid beta(42) activates a G-protein-coupled chemoattractant receptor, FPR-Like-1

Amyloid beta (A beta) is a major contributor to the pathogenesis of Alzheim er's disease (AD). Although A beta has been reported to be directly neuroto xic, it also causes indirect neuronal damage by activating mononuclear phag ocytes (microglia) that accumulate in and around senile plaques. In this st udy, we show that the 42 amino acid form of beta amyloid peptide, A alpha ( 42), is a chemotactic agonist for a seven-transmembrane, G-protein-coupled receptor named FPR-Like-1 (FPRL1), which is expressed on human mononuclear phagocytes. Moreover, FPRL1 is expressed at high levels by inflammatory cel ls infiltrating senile plaques in brain tissues from AD patients. Thus, FPR L1 may mediate inflammation seen in AD and is a potential target for develo ping therapeutic agents.