Reduction of plasma glutamyl aminopeptidase activity in sporadic Alzheimer's disease

Previously, we hypothesized that aminopeptidase-catalyzed proteolysis may limit the rate of beta-amyloid catabolism in brain and that reduction of a certain aminopeptidase activity may lead to deposition of peptidic metabolites represented by beta-amyloid and thus to Alzheimer's disease (AD), To explore this possibility in clinical situations and to 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 controls collected in two independent medical institutions. We found that only plasma glutamyl aminopeptidase activity was significantly and consistently lower in AD patients. Although the mechanism leading to such a biochemical change in plasma remains to be elucidated, the results provide support for the aminopeptidase hypothesis and indicate that the enzyme activity may potentially be used as a diagnostic/predictive marker for AD. (C) 1997 Academic Press.