A novel metalloprotease in rat brain cleaves the amyloid precursor protein of Alzheimer's disease generating amyloidogenic fragments

A Golgi and plasma membrane-enriched fraction was isolated from rat brain and incubated at 37 degrees C at pH 7.2 to investigate the breakdown of endogenous amyloid precursor protein (APP). The degradation of APP was accompanied by the concomitant generation of A-beta-containing C-terminal fragments in a time-dependent manner. Findings indicated that a novel Zn2+-dependent metalloprotease activity associated with a Golgi and plasma membrane-enriched fraction can break down endogenous APP to produce A-beta containing C-terminal fragments.