Although PS1/APP bigenic mice have been frequently studied, the parental presenilin lines have been less studied, likely because of their lack of a robust AD-like pathology. However, PS1 and PS2 FAD mutant lines show exaggerated hippocampal damage after kainate-induced excitotoxicity,27,32,33 and PS1 FAD mutants render animals more sensitive to trimethyltin-induced hippocampal damage.34 Excessive neuronal loss in the entorhinal cortex also occurs in mice harboring the deltaE9 PS1 FAD mutation after lesioning of the perforant path.35 Increased protein oxidation and lipid peroxidation have also been reported in PS1 FAD mutant brain.36,37 Several studies have documented impaired hippocampal neurogenesis in adult PS1 FAD mutant mice,38–42 and recently, an age-dependent impairment of spine morphology and synaptic plasticity in hippocampal cornu ammonis 1 neurons of a PS1 transgenic mouse model has been described.43 Age-related neurodegenerative changes with neuronal loss have been reported in one PS1 FAD mutant line,44 and age-related NFT-like inclusions have been described in a PS1 knock-in line.45 Recently, a microvascular pathology that is highly reminiscent of the microvascular pathology found in AD has also been described.46 Thus, presenilin FAD mutant mice
