We don’t understand Alzheimer, its origin and disease mechanisms. The absence of disease-modifying treatments for Alzheimer today is due to the amyloid hypothesis, a misguided hypothesis of Alzheimer’s disease etiology, which has dominated Alzheimer research, drug development, and clinical trials for 30 years. However, the hypothesis is not dead yet, as exemplified by the recent resurrection of clinical trials with aducanumab. Recent advances in Alzheimer research include astrocytes, synaptic function and glutamate signaling. Many studies indicate EAAT2 as a promising target in drug discovery and clinical development for novel therapies in Alzheimer’s disease, and other neurologic and psychiatric diseases.