In summary, our data revealed that LY3000328 could alleviate the neuroinflammation response, decrease Aβ deposition, and rescue the learning and memory deficits in APP/PS1 mice via the CX3CL1‐CX3CR1 axis and JAK2‐STAT3 pathway, suggesting that CTSS has great potential for use as an effective target for treating AD. This evidence concerns the gene JAK2 and Alzheimer disease.