Alterations of Spatial Memory and Gut Microbiota Composition in Alzheimer's Disease Triple-Transgenic Mice at 3, 6, and 9 Months of Age.

Alzheimer's disease (AD) is a progressive neurological disease. Gut microbial dysbiosis is associated with AD. This study involves the comparative assessment of spatial learning, β-amyloid peptide accumulation, and fecal microbiota alterations in 3×Tg-AD mice from 3 age groups: AD asymptomatic stage (3 m), presymptomatic stage (6 m), and the symptomatic stage of AD (9 m). We demonstrate that spatial memory deficits, brain Aβ accumulation, and weight gain in 3×Tg-AD mice gradually appear after 6 months of age. However, the total gut bacterial counts underwent changes from 3 to 6 months of age and were further altered at 9 months of age. Importantly, changes in gut bacteria abundance of Desulfobacterota and Actinobacteriota phyla in 6-month-old mice preceded apparent spatial memory deficits. In summary, Changes in the gut microbial community are one of the mechanisms of early AD pathology.