Alzheimer’s disease is a devastating neurodegenerative disease and the most common form of dementia that currently affects 55 million people globally. Alzheimer’s disease is characterized by loss of memory, changes in mood and behavior and the inability to perform daily tasks. Besides its clinical symptoms, Alzheimer’s disease comprises enormous socioeconomic burdens as well as social and psychological difficulties for caretakers and families. Inflammation, a major hallmark of Alzheimer’s disease, has recently emerged as a potential therapeutic target. In this study we show that targeting TNF-α, a master regulator of the immune system, and its receptors, results in improvements in cognitive functions and attenuation of Alzheimer-related neuropathology in a mouse model of Alzheimer’s disease.