There is prior evidence for impaired glutamate homeostasis in AD.[53] Glutamate homeostasis plays essential roles in dendritic spine morphology, the postsynaptic proteins that regulate dendritic spine morphology, glutamate signaling, and the physiology of glutamate synaptic.[6] Our study provides the first demonstration that PEDF plays an indispensable physiological role in glutamate homeostasis by modulating astrocytic GLT‐1. This evidence concerns the gene SERPINF1 and Alzheimer disease.