PLG and Alzheimer disease: Nonetheless, in AD animal models where endogenous tPA was genetically reduced, a greater accumulation of Aβ was observed, in association with synaptic dysfunction and memory deficits.39 In addition, it was shown that tPA‐mediated plasmin activity declines throughout the brain, causing Aβ deposition during aging.40 Similarly, in humans, it was found that tPA activity is reduced in the brain of AD patients as compared to controls41 and negatively correlates to Aβ levels,42 while tPA protein levels are unchanged41 or increased.43