In this study, we generated a mouse model with hyperactive autophagy by knocking-in a point mutation F121A to Beclin 1/Becn1, and found that Becn1F121A-mediated autophagy hyperactivation reduces brain amyloid accumulation, ameliorates cognitive deficits, and improves survival rates in Alzheimer’s mouse models. Here, BECN1 is linked to Cognitive impairment.