The mechanisms underlying the increase in P2X7R in disease remain unclear but may reflect damage-induced increases in AD brain of specific protein 1 (SP1) (Citron et al., 2008), a transcription factor that regulates the expression of P2X7R in astrocytes and microglia (Garcia-Huerta et al., 2012, Qin et al., 2017). Here, SP1 is linked to Alzheimer disease.