Inhibition of PAI-1 activity or deletion of the PAI-1 gene reduced brain Aβ load and improved memory in APP/PS1 mice [15,100,107,109], suggesting a pivotal role of PAI-1 in the pathophysiology of AD, although the mechanism by which PAI-1 promotes AD-liked neuropathophysiology remains unclear. This evidence concerns the gene PSEN1 and Alzheimer disease.