A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer's Disease

beta-Amyloid (A beta), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer's disease (AD) in the brain. In addition, A beta accumulates in skeletal muscle cells in individuals with sporadic inclusion body myositis (sIBM), an age-related muscle disease. Because of the socioeconomic burden associated with age-related diseases, particularly AD, there has been considerable emphasis on studying potential therapeutic strategies. The high-fat, low carbohydrate ketogenic diet has been used extensively to treat refractory childhood epilepsy and has been studied as a potential treatment for other neurological diseases, including Parkinson's disease and AD. In this study, we fed young APP/PS1 knock-in mice, which have a whole body knock-in of AD-related genes, a ketogenic diet and determined the effect on A beta levels in the brain and skeletal muscle, as well motor performance and oxidative stress. A beta and its precursor, the beta-C-terminal fragment of amyloid precursor protein (CTF beta), were unchanged overall in both the brain and quadriceps after 1 month on the ketogenic diet, and there was no effect on nitrotyrosine, a product of oxidative stress. The ketogenic diet improved performance on the Rota-rod apparatus (p=0.007), however. These data indicate that the ketogenic diet may have some efficacy in the treatment of both neurologic and muscle diseases though the underlying mechanisms do not involve amelioration of A beta pathology. (C) 2013 Elsevier B.V. All rights reserved.