Since changes in the KV2.1 function could be critical for the homeostatic regulation of neuronal excitability, in the present study we investigated any possible modulation of the KV2.1 protein expression and activity in the Tg2576 mouse model of AD, which expresses a human APP gene carrying the double Swedish mutation (KM670/671NL) and produces elevated levels of Aβ1–42 [46]. This evidence concerns the gene KCNB1 and Alzheimer disease.