Fig. 1.

The “eat me” signal is the key to recognizing unnecessary or inappropriate synapses during neurodevelopment. In contrast, the ‘‘don’t eat me’’ signal serves as a negative regulator of synaptic pruning to avoid excessive elimination of synapses [4]. Using a microglial SIRPα conditional knockout mouse model, Ding et al. [9] provided evidence that SIRPα deletion induces significant synapse loss during early neurodevelopment. In addition, they found that the expression of microglial SIRPα significantly decreased in Alzheimer’s disease (AD) pathology and demonstrated that the decreased expression of microglial SIRPα resulted in excessive microglial engulfment of synapses and exacerbated the cognitive impairment in AD.