REDUCTION OF PLASMA GLUTAMYL AMINOPEPTIDASE ACTIVITY IN SPORADIC ALZHEIMERS-DISEASE

Previously, we hypothesized that aminopeptidase-catalyzed proteolysis may limit the rate of beta-amyloid catabolism in brain and that reduct ion of a certain aminopeptidase activity may lead to deposition of pep tidic metabolites represented by beta-amyloid and thus to Alzheimer's disease (AD), To explore this possibility in clinical situations and t o seek, a possible biochemical marker for the disease, eye quantitated four classes of aminopeptidase activities in cerebrospinal fluids and heparinized plasma, from sporadic AD patients and age-matched control s collected in two independent medical institutions. We found that onl y plasma glutamyl aminopeptidase activity was significantly and consis tently lower in AD patients. Although the mechanism leading to such a biochemical change in plasma remains to be elucidated, the results pro vide support for the aminopeptidase hypothesis and indicate that the e nzyme activity may potentially be used as a diagnostic/predictive mark er for AD. (C) 1997 Academic Press.