In discrepancy with these studies, in vivo studies with mouse models of AD have revealed that chronic elevation of Aβ actually decreases tPA activity by enhancing the inhibitory effect of PAI-1 on tPA, and that the intracerebral injection of Aβ causes neuronal degeneration in animals genetically deficient in either tPA or plasminogen [162]. The gene discussed is SERPINE1; the disease is Alzheimer disease.