Abstract: Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive decline, synaptic dysfunction, and neurotransmitter imbalance. Novel neuromodulation approaches, both non-invasive and invasive, show promising potential for restoring neural circuit integrity and improving cognition. This review aims to elucidate the relationship between neuromodulation, neural network circuits, and neurotransmitters. It systematically synthesizes recent advances in neuromodulation techniques, focusing on their ability to modulate four critical neurotransmitter systems: cholinergic, glutamatergic, GABAergic, and monoaminergic systems. Additionally, this review establishes a critical association between neurotransmitter regulation and synaptic plasticity mechanisms, proposing a novel “circuit-transmitter” triad framework for intervention. It represents the first systematic integration of the neurotransmitter regulation mechanisms of various neuromodulation techniques while evaluating their clinical viability for Alzheimer’s disease intervention. Beyond established targets, this review identifies the hippocampus-thalamus axis, linked via direct entorhinal-thalamic projections, as a promising focus for ultrasonic neuromodulation research. 

Key words: Alzheimer’s disease, deep brain stimulation, default mode network, neurology, neuromodulation technologies, neurotransmitter agents, transcranial direct current stimulation, transcranial magnetic stimulation, transcranial ultrasound stimulation, vagus nerve stimulation