NEUTRAL ENDOPEPTIDASE CAN HYDROLYZE BETA-AMYLOID(1-40) BUT SHOWS NO EFFECT ON BETA-AMYLOID PRECURSOR PROTEIN-METABOLISM

High performance liquid chromatographic analyses of incubations of bet a-amyloid(1-40) with neutral endopeptidase revealed at least nine prod uct peaks, indicating that neutral endopeptidase can cleave P-amyloid at multiple sites. Mass spectroscopic analysis of hydrolyzed P-amyloid identified at least five cleavage sites, between residues Glu(3)-Phe( 4), Gly(9)-Trp(10), Phe(19)-Phe(20), Ala(30)-Ile(31), and Gly(33)-Leu( 34). In contrast, amyloid precursor protein metabolism in Neuro2A cell s was unaffected by the expression of recombinant neutral endopeptidas e in the same cells or by the addition of a secreted form of neutral e ndopeptidase to spent Neuro2A cell media.