APP and Cognitive impairment: The significance of cholinergic signaling in AD was long recognized.531 A hallmark of cognitive impairment is the loss of basal forebrain cholinergic neurons, which is driven by APP processing, Aβ deposition, tau hyperphosphorylation and dysregulated immune response.527 At present, there is a limited number of studies examining the potential of microbiome-based therapeutics for modulating the cholinergic system in AD, but the evidence available supports their beneficial effects on the cholinergic system.