MAPT and memory impairment: Interestingly, whereas tau has been placed downstream of Aβ in a pathocascade, providing support for the amyloid cascade hypothesis [30, 55], a reduction in endogenous tau levels in APP transgenic mice was found to reverse memory impairment, reduce susceptibility to experimentally induced excitotoxic seizures, and decrease early mortality, without altering Aβ levels or plaque load [81].