Implications of the Gut Microbiome in Alzheimer’s Disease: A Narrative Review

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with its prevalence doubling approximately every decade. It is a significant contributor to disability-adjusted life-years in individuals aged 50 and older, impacting a substantial portion of this population globally. The pathophysiology of AD is primarily explained by two hypotheses: the amyloid cascade hypothesis and the tau hypothesis. While the amyloid cascade hypothesis is widely accepted as the main contributor to AD, both mechanisms promote neuroinflammation by driving the formation of amyloid-beta (Aβ) plaques and tau tangles, which are key features of the neurodegenerative process. Recent studies highlight the critical role of the gut microbiome (GMB) in the progression of AD. Gut dysbiosis has been linked to neuroinflammation, altered Aβ metabolism, blood-brain barrier disruption, and changes in neuroactive metabolites. Targeting the GMB offers potential therapeutic avenues aimed at restoring microbial balance and mitigating the effects of dysbiosis. The gut-brain axis, crucial for neurological health, remains underexplored in AD, especially since current research is limited to animal models and small human studies, leaving uncertainty about specific gut bacteria's roles in AD. Currently, pharmacological treatments for AD include cholinesterase inhibitors and memantine. This review discusses newer and emerging treatments targeting Aβ and tau pathology, alongside microbiome-based interventions. Larger, human-based studies with diverse populations are essential to establish the therapeutic efficacy of these microbiome-targeted treatments and their long-term impact on AD management.