The prevalence of age-related neurodegenerative disorders, particularly Alzheimer’s disease (AD), has dramatically increased, affecting millions of individuals worldwide. The increasing AD incidence, reducing age of onset and heterogeneity suggest that genetic and environmental factors may be implicated in AD pathogenesis, including contributions of the microbiota. Indeed, the gut microbiome is vital for homeostasis, since dysregulation in gut microbial composition and function have been linked to alterations in immune, metabolic, and neuronal responses. However, the mechanisms by which the microbiome could impact the onset and progression of AD remain elusive. Therefore, we hypothesize that compositional and/or functional microbiome alterations in the gut may have a causal impact on AD development. This, together with results linking the microbiome-derived metabolites to alterations of the central nervous system, suggests a potential means of communication by which metabolic products from gut microbes could modify the brain, impacting the course of AD. Thus, we propose to study how the gut microbiome affects AD development, attempting to identify and characterize beneficial versus disease-associated microbiome, and how changes in bacterial composition and/or metabolites may affect the brain function in an AD genetic murine model, and further extend our findings to a human setting.