Our preclinical study in TDP-43A315T mice demonstrates that bioenergetic stress and AMPK signalling is attenuated through a high-fat diet at the level of the diseased tissue, and suggests that nutritional intervention using a high-fat and high-calorie diet might represent a therapeutic avenue in individuals with TDP-43 ALS. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.