Microglia-Neuron Interactions in Alzheimer’s Disease

Abstract: Alzheimer's disease (AD) is a progressive disease characterized by significant cognitive decline, posing a substantial threat to life. Neuronal loss and dysfunction are responsible for the cognitive decline and behavioral disturbances observed in AD. Microglia are increasingly recognized for shaping the fate of neurons. However, the role of microglia-neuron interaction in neuronal degeneration of AD remains largely unclear. This review discusses microglia-mediated excessive synaptic pruning and microglia-neuron metabolic coupling in the neuronal degeneration of AD. It also summarizes the role of microglia-neuron interactions in classical pathogenic hypotheses such as the amyloid cascade, tau protein, neuroinflammation, and metal ions. It is found that microglia can serve as protectors of neurons, yet they also exacerbate neuronal damage under stress stimulation. This bidirectional modulation of microglia-neuron interaction provides a novel direction for rescuing AD neurons.