In this study, we tested a hypothesis that aging-related increase in PAI-1 contributes to brain cell senescence and thus the neuropathophysiology during aging and in LOAD, using senescence accelerated murine prone 8 (SAMP8) mice, which harbor many behavioral and histopathological signatures of AD [21-27], and brain tissue samples from LOAD patients and age-matched healthy controls. This evidence concerns the gene SERPINE1 and Alzheimer disease.