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, we quantitated four classes of aminopeptidase activities in cerebrospinal fluids and heparinized plasma from sporadic AD patients and agematched 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.