Moreover, in amyloid-based models of AD, TNF-α elevation promotes glutamatergic hyperactivity and the excitatory/inhibitory (E/I) imbalance in hippocampal circuits, with TNF-α blockade by XPro1595 preventing early synaptic deficits (Cavanagh et al., 2016) Similar hyperexcitability and LTP impairment were observed in TREM2R47H KI rats, linking microglial dysfunction to TNF-α-mediated synaptic alterations (Ren et al., 2020a). Here, TNF is linked to Alzheimer disease.