Excessive urokinase-type plasminogen activator activity in the euglobulin fraction of patients with Alzheimer-type dementia

We examined the activity of the serine protease urokinase-type plasminogen activator (uPA) present in the euglobulin fraction of plasma from 17 demented patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 10 healthy controls. Euglobulin protein fractions were separated by electrophoresis and gels were incubated at the surface of plasminogen-rich casein-agarose underlays. The degradative activity of uPA in this system was measured by densitometric analysis. In 8 17 (47%) patients with AD we observed an excessive uPA activity (> 200 mIU/ml). In contrast, only 2 12 (16%) patients with VD and 1 10 (10%) control subjects revealed a comparable increase in circulating uPA activity. Further evaluation of dementia stage in patients with AD allow us to associate high levels of uPA activity with severity of disease. uPA levels were significantly elevated (2.8-fold increase) in AD patients with severe cognitive and memory impairments (Alzheimer Disease Assesment Scale) with respect to controls, VD patients or AD patients with moderate cognitive and memory impairments ( P < 0.001, ANOVA). Our data suggest that the anormalities in circulating fibrinolytic enzymes could be correlated with the severity of dementia. In light of this findings, the free uPA activity in euglobulin plasma fraction should be considered a marker of serious damage in patients with AD.