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Neurometabolic roles of ApoE and Ldl-R in mouse brain

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Abstract

Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer’s disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life.

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Acknowledgments

This work was supported in part by National Institutes of Health grants NS072241 to M.J.W. and DK084171 to G.W.W.

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Authors and Affiliations

  1. Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Jieun Lee, Joseph Choi & Michael J. Wolfgang

  2. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    G. William Wong

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  1. Jieun Lee
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  2. Joseph Choi
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  3. G. William Wong
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  4. Michael J. Wolfgang
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Correspondence to Michael J. Wolfgang.

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Lee, J., Choi, J., Wong, G.W. et al. Neurometabolic roles of ApoE and Ldl-R in mouse brain. J Bioenerg Biomembr 48, 13–21 (2016). https://doi.org/10.1007/s10863-015-9636-6

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  • DOI: https://doi.org/10.1007/s10863-015-9636-6

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