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 beta-amyloid(1-40) with neutral endopeptidase revealed at least nine product 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 cells was unaffected by the expression of recombinant neutral endopeptidase in the same cells or by the addition of a secreted form of neutral endopeptidase to spent Neuro2A cell media.