In a group of pre-clinical AD patients, with normal cognitive function ante-mortem coupled to AD neuropathology at autopsy, there was evidence of autophagy impairment although no changes in the PI3K-AKT-mTOR pathway were found, suggesting that disrupted autophagy may be an early event in Aβ deposition (Tramutola et al., 2015). The gene discussed is AKT1; the disease is Alzheimer disease.