Overall, higher connectivity was observed among neuron differentiation processes, neurogenesis, proteolysis, cell death, autophagy, and endocytosis in the brain tissue of 5xFAD*APN KO compared to 5xFAD WT mice, suggesting the above‐related process may play a crucial role underlying APN deficiency accelerated cognitive impairment. Here, ANPEP is linked to Cognitive impairment.