Decreases in protease nexins in Alzheimerʹs disease brain

A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid β protein precursor (AβPP) was observed in selected regions of Alzheimerʹs disease (AD) brains as compared to those of aged-matched controls. Correlative analysis indicated a relationship between PN-1 reduction and the severity of pathologic alterations. A statistically 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 regulate neurite outgrowth, it is possible that abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite formation. The presence of clusters of dystrophic neurites around the capillaries suggests that bloodbrain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/AβPP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the ability of PN-2/AβPP to protect neurons against the toxic effects of the Aβ.