Fatty‐acid amide hydrolase inhibition mitigates Alzheimer’s disease progression in mouse models of amyloidosis

Abstract The endocannabinoid N‐arachidonoylethanolamine (AEA) is a pro‐homeostatic bioactive lipid known for its anti‐inflammatory, anti‐oxidative, immunomodulatory, and neuroprotective properties, which may contrast/mitigate Alzheimer’s disease (AD) pathology. This study explores the therapeutic potential of targeting fatty acid amide hydrolase (FAAH), the major enzyme degrading AEA, in mouse models of amyloidosis (APP/PS1 and Tg2576). Enhancing AEA signaling by genetic deletion of FAAH delayed cognitive deficits in APP/PS1 mice and improved cognitive symptoms in 12‐month‐old AD‐like mice. Chronic pharmacological FAAH inhibition fully reverted