DECREASES IN PROTEASE NEXINS IN ALZHEIMERS-DISEASE BRAIN

A marked and significant reduction of protease nexin-1 (PN-1) and PN-2 /amyloid beta protein precursor (A beta PP) was observed in selected r egions of Alzheimer's disease (AD) brains as compared to those of aged -matched controls. Correlative analysis indicated a relationship betwe en PN-1 reduction and the severity of pathologic alterations. A statis tically significant inverse correlation was noted between the level of PN-1 activity and the density of tau-positive dystrophic neurites in the hippocampus. In view of the ability of thrombin and PN-1 to regula te neurite outgrowth, it is possible that abnormal thrombin and PN-1 i nteractions may play a role in dystrophic neurite formation. The prese nce of clusters of dystrophic neurites around the capillaries suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the abi lity of PN-2/A beta PP to protect neurons against the toxic effects of the A beta.