PLG and Alzheimer disease: However, human cohort studies showed no significant alteration in the net enzymatic activities of plasmin in AD, although there was an observed increase in the mRNA level of both activators (tPA and uPA) and inhibitors (PAI-1 and α2-antiplasmin) of the plasminogen system, with increases more at the late Braak stage (Barker et al., 2012).