To further investigate the role of microglial H4R in AD, we silenced Hrh4 expression specifically in microglia within the cortex and hippocampus using a lentiviral vector encoding Hrh4‐targeted shRNA (Lenti–Hrh4–shRNA) under the control of a fractalkine receptor gene promoter Cx3cr1, which selectively labels microglia.[73, 74, 75] Similarly, Lenti–Hrh4–shRNA or Lenti–scr‐shRNA was injected into the cortex and hippocampus regions (CA1 and CA3) of 6 months old APP/PS1 mice (Figure S12A, Supporting Information). Here, PSEN1 is linked to Alzheimer disease.