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

Tina L. Beckett, Christa M. Studzinski, Jeffrey N. Keller, M. Paul Murphy, Dana M. Niedowicz

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

β-Amyloid (Aβ), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer's disease (AD) in the brain. In addition, Aβ 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 Aβ levels in the brain and skeletal muscle, as well motor performance and oxidative stress. Aβ and its precursor, the β-C-terminal fragment of amyloid precursor protein (CTFβ), 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 Aβ pathology.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalBrain Research
Volume1505
DOIs
StatePublished - Apr 10 2013

Bibliographical note

Funding Information:
We would like to thank Dr. Chris Holler and Robin Webb for tissue collection and Dr. Todd Golde for providing Aβ antibodies. Supported by NIH ( AG005119 , NS058382 ), The Coins for Alzheimer's Research Trust and the Alzheimer's Association ( IIRG-10–172905 ).

Keywords

  • Alzheimer's disease
  • Amyloid
  • Inclusion body myositis
  • Ketogenic diet

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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