Taken together, these data indicate depletion of PEDF increases the concentration of glutamate at synapses in the early stage of AD by reducing the expression of GLT‐1 astrocytes, and these changes significantly contribute to the age‐related progression of AD pathology, including impaired synaptic plasticity, neuronal loss, amyloid β production and tau phosphorylation. The gene discussed is SLC1A2; the disease is Alzheimer disease.