Excessive microglial phagocytosis activity of synapses was decreased after knockout of microglial AIM2, which was associated with inhibiting complement activation.<h4>Conclusion</h4>Our results demonstrated that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease. Here, AIM2 is linked to Alzheimer disease.