Comparison of major cortical aminopeptidase activity in normal brain and brain from patients with Alzheimer's disease

Abstract

In order to develop a greater understanding of the importance of peptide catabolism in the intracellular protein degradation process in normal and pathological human brain, we have undertaken a systematic investigation of the aminopeptidase group of enzymes. Although a wide range of aminoacyl-7-amino-4-methylcoumarin derivatives (which are used to measure aminopeptidase activity) were hydrolysed by normal human cortical soluble extract, fractionation of the latter via anion exchange and gel filtration chromatography resolved only 4 separable aminopeptidase types (activity relative to alanyl aminopeptidase in parenthesis): alanyl (EC 3.4.11.14, 100%); arginyl (2 isoenzymes, EC 3.4.11.6, 15%); pyroglutamyl (EC 3.4.19.3, 4%); and leucyl (EC 3.4.11.1, 1%). Thus approx. 80% of the total soluble aminopeptidase activity in normal human cerebral cortex can be accounted for by a single enzyme, the major cortical aminopeptidase. The activity of this enzyme was measured in the soluble fraction prepared from 4 cortical regions (occipital, frontal, temporal and parietal) in a series of 8 patients with Alzheimer's disease and compared with corresponding data in 8 control normal patients. Although enzyme activity varied in these cortical regions, the activity in corresponding brain areas in the Alzheimer's disease and normal groups was very similar. These findings suggest that the characteristic neurodegeneration associated with Alzheimer's disease does not result from altered activity of the major cortical aminopeptidase in the cortical tissue of patients with this disorder.