This study reveals novel data concerning the possible role of the GABA transporter GAT3/4 in AD, and provides a mechanistic insight into the pathophysiology of AD in terms of synaptic imbalance governed by astrocyte-specific mechanisms that contribute to altered background tonic inhibition in the first knock-in APPNL-F/NL-F mouse model of AD. The gene discussed is SLC6A11; the disease is Alzheimer disease.