Study Title
Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer’s models
Cell Reports

Priya Rangan, Fleur Lobo, Edoardo Parrella, Nicolas Rochette, Marco Morselli, Terri-Leigh Stephen, Anna Laura Cremonini, Luca Tagliafico, Angelica Persia, Irene Caffa, Fiammetta Monacelli, Patrizio Odetti, Tommaso Bonfiglio, Alessio Nencioni, Martina Pigliautile, Virginia Boccardi, Patrizia Mecocci, Christian J Pike, Pinchas Cohen, Mary Jo LaDu, Matteo Pellegrini, Kyle Xia, Katelynn Tran, Brandon Ann, Dolly Chowdhury, Valter D Longo


The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer’s disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

September 27, 2022
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