Brain membrane serine protease activity in human cortex compared with rat: implication for Alzheimer's disease.
Cerebral cortex from humans and rats was extracted sequentially with detergent-containing and low-ionic-strength buffers. The resulting pellet 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 protein-like immunoreactivity (APPLIR) of 116 kD approximate apparent molecular mass. The effectiveness of various enzyme preparations to degrade 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 brain 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 studying proteolytic activity to explain the deposition of beta-amyloid protein in this disease.
Institute of Neurology, Guy's Hospital Campus, London, UK.
G C
GC
Stratmann
M T
MT
Webster
P T
PT
Francis
A W
AW
Procter
D M
DM
Bowen
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D003128:Coma / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008566:Membranes / Q000201:enzymology; D008875:Middle Aged; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012697:Serine Endopeptidases / Q000378:metabolism*; D014018:Tissue Distribution
D016564:Amyloid beta-Protein Precursor; D012697:Serine Endopeptidases