APP and Alzheimer disease: Though no model of AD fully recapitulates the human disease [116], APP.PS1 mice are characterized by: (1) high production of amyloid Aβ peptides in brain and accumulation of amyloid plaques by 4–6 months of age [117]; (2) cognitive impairments [118,119,120,121,122]; (3) cholinergic defects [123,124,125,126,127,128]; and (4) evidence of abnormal methylation of several genes [129].