Tissue Plasminogen Activator Requires Plasminogen to Modulate Amyloid‐β Neurotoxicity and Deposition

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Abstract
Tissue plasminogen (plgn) activator (tPA) modulates neuronal death in models of stroke, excitotoxicity, and oxidative stress. Amyloid-β (Aβ) appears central to Alzheimer's disease and is neurotoxic to neurons in vitro. Here, we evaluate tPA effects on Aβ toxicity. We report that tPA alone had no effect on Aβ toxicity. However, in combination with plgn, tPA reduced Aβ toxicity in a robust fashion. Moreover, the combined tPA and plgn treatment markedly inhibited Aβ accumulation. The addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to a sample of tPA, plgn, and Aβ resulted in a marked reduction of Aβ degradation. We interpret the actions of tPA and plgn within the context of the ability of plasmin to degrade Aβ.