In AD, Aβ deposition and p-tau accumulation induce parenchymal innate immune activation, affecting the integrity of the blood–brain barrier (BBB), CSF/ISF flow and lymphatic drainage, further leading to the antigen-presenting microglia, expansion of IFN-reactive, the increase of inflammatory cytokines and antigen accumulation, as well as parenchymal T-cell infiltration, T cell receptor (TCR) clonal expansion in the brain parenchyma and border areas [4]. The gene discussed is MAPT; the disease is Alzheimer disease.