Targeting Neuroinflammation And The Gut–Brain Axis In Alzheimer's Disease: Emerging Mechanisms and Therapeutic Perspectives

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid-β accumulation and tau pathology coexist with sustained neuroinflammatory activation. Increasing evidence indicates that neuroinflammation is not a secondary response to protein aggregation but a central driver of synaptic dysfunction, neuronal loss, and cognitive decline. In parallel, the gut–brain axis has emerged as a critical regulator of neuroimmune homeostasis. Alterations in gut microbiota composition, intestinal barrier integrity, and microbial metabolite production influence systemic inflammation, blood–brain barrier permeability, and microglial activation, thereby shaping Alzheimer’s disease progression. This review integrates recent advances in neuroinflammation research with emerging insights into gut–brain axis dysregulation, highlighting mechanistic pathways and therapeutic strategies that target immune–microbial interactions. Modulation of neuroinflammation through gut-directed and immune-focused interventions represents a promising avenue for disease modification beyond traditional amyloid-centric approaches.