Gut-brain axis in Alzheimer's disease: neural and immune circuits linking peripheral dysbiosis to neurodegeneration.

Alzheimer's disease (AD) is increasingly conceptualized as a system-level disorder shaped by bidirectional communication between the gut and the brain. The gut-brain axis (GBA) integrates neural, immune, and metabolic signaling pathways that influence central neuroinflammation and proteopathy. Recent mechanistic studies demonstrate that gut dysbiosis alters microbial metabolite profiles, promotes microglial immunometabolic reprogramming, and facilitates amyloid and tau pathology. The vagus nerve functions as a bidirectional conduit enabling neural transmission of inflammatory signals and tau propagation directly. Emerging evidence implicates microbiota-derived extracellular vesicles as mediators of peripheral-to-central immune modulation. Human gut-brain organoid platforms now allow causal interrogation of these interactions in physiologically relevant systems. Together, these advances reframe AD as a disorder of dysregulated neural-immune communication and identify the GBA as a tractable therapeutic target.