BRAIN MEMBRANE SERINE-PROTEASE ACTIVITY IN HUMAN CORTEX COMPARED WITHRAT - IMPLICATION FOR ALZHEIMERS-DISEASE

Cerebral cortex from humans and rats was extracted sequentially with d etergent-containing and low-ionic-strength buffers. The resulting pell et was extracted with detergent/high-ionic-strength buffer to yield a soluble enzyme preparation. This was incubated with substrate prepared from rat cerebral cortical membranes containing amyloid precursor pro tein-like immunoreactivity (APPLIR) of 116 kD approximate apparent mol ecular mass. The effectiveness of various enzyme preparations to degra de APPLIR was: routine-post-mortem (pm)-delay human samples > rat pup > short-pm-delay human samples >> adult rat. In incubations with human samples only a 100-kD product accumulated. The activity in human brai n was inhibited by phenylmethylsulphonylfluoride, insensitive to Ca2+, correlated with pyramidal neurone numbers but not those of astrocytes and was not significantly higher in Alzheimer's disease compared with controls. These data are discussed in terms of other approaches for s tudying proteolytic activity to explain the deposition of beta-amyloid protein in this disease.