Thus, to directly assess the function of physiological enhancement of autophagy in vivo, we generated and characterized a unique mouse model of constitutively active autophagy caused by a single knockin mutation (F121A) in Becn1. We crossed these autophagy-hyperactive mice with the 5XFAD transgenic AD mice, which overexpress a combination of 5 familial Alzheimer’s disease (FAD) mutations in human APP and human PS1 (presenilin 1) proteins and show early amyloid deposition beginning at 2 months of age and cognitive decline at 6 months of age [25]. This evidence concerns the gene BECN1 and Alzheimer disease.