In contrast to Tg2576 mice, most mouse models used to study hyperexcitability in AD contain more than 1 mutation in either APP cleavage sites or the secretases that cleave APP (e.g. APPSwe/Indiana, APPSwe/presenilin 1 (PS1) Δe9), resulting in accelerated β-amyloid deposition10. Here, PSEN1 is linked to Alzheimer disease.