A Fasting-mimicking diet reduces neuroinflammation/Nox2 to attenuate cognitive decline in Alzheimer's models.

The wide-acting effects of FMDs on metabolic, inflammatory and regenerative pathways leading to reduced pathology or risk factors for various diseases in mice and humans, has the potential to be effective against Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models and were overall more effective than protein restriction cycles. In 3xTg mice, long-term FMD cycles reduced hippocampal Abeta load and hyperphosphorylated tau, enhanced genesis of Type I/II neural stem cells, decreased microglia number and activity, and reduced expression of neuroinflammatory genes including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin displayed improved cognition and reduced microglia activation compared to controls. Preliminary clinical data indicates that FMD cycles are feasible for testing in AD patients.