The major findings of this study include 1) the gut is a major source of Aβ peptides, with its production further enhanced by aging process and APP/PS1 mice-derived GM; 2) transmission of gut Aβ42 to the brain is mainly via blood, instead of the vagal nerve, in aged mice; 3) transplanting fecal bacteria of aged APP/PS1 mice can provoke functional and pathological alterations in young mice, mimicking early AD pathology. This evidence concerns the gene PSEN1 and Alzheimer disease.