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Metabolomics and mitochondrial dysfunction in Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is characterized by cognitive impairment, progressive neurodegeneration, and Aβ accumulation. Aβ oligomers can lead to synaptic damage via alterations in glutamate receptors and excitotoxicity, as well as mitochondrial dysfunction. AD is associated with various biological indicators, including (1) predisposing factors such as genetic risk factors, (2) laboratory markers such as Aβ and tau protein, and (3) diagnostic markers such as MRI and PET findings. However, these markers are not confirmed, invasive, or expensive. In the present study, we employed nuclear magnetic resonance (NMR) methods that are inexpensive, time-efficient, and can be performed using samples obtained from various easily accessible sources such as cerebrospinal fluid, plasma, and peripheral tissue, thus highlighting the clinical utility of this approach. NMR analyses of blood metabolites showed that glutamine, glutamate, leucine, oxaloacetate, aspartate, isoleucine, and 3-hydroxyisovalerate are increased in patients with AD compared with control individuals. These metabolites seem to be related to mitochondrial dysfunction. Our data indicated that 3-hydroxyisovalerate, which is linked to known pathologic processes associated with mitochondrial dysfunction and accelerated neurodegeneration, was increased in the blood samples of patients with AD.

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    Authors and Affiliations

    1. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 46241, Korea

      Dong Hee Kim, Jeong-An Gim & Heui-Soo Kim

    2. Department of Psychiatry, Hyungju Hospital, Yangsan, 50509, Korea

      Dong Hee Kim

    3. Genetic Engineering Institute, Pusan National University, Busan, 46241, Korea

      Jeong-An Gim & Heui-Soo Kim

    4. Department of Chemistry, Center for Proteome Biophysics and Chemistry Institute for Functional Materials, Pusan National University, Busan, 46241, Korea

      Dahye Yoon & Suhkmann Kim

    Authors
    1. Dong Hee Kim
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    2. Jeong-An Gim
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    3. Dahye Yoon
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    4. Suhkmann Kim
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    5. Heui-Soo Kim
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    Correspondence to Heui-Soo Kim.

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    DHK declares that he has no conflict of interest. J-AG declares that he has no conflict of interest. DY declares that she has no conflict of interest. SK declares that he has no conflict of interest. H-SK declares that he has no conflict of interest.

    Ethical approval

    This study was performed in accordance with South Korea laws and the guidelines of the Ethics Committee at the Woosan Medical Foundation.

    Additional information

    Dong Hee Kim, Jeong-An Gim and Dahye Yoon have contributed equally to this work.

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    Kim, D.H., Gim, JA., Yoon, D. et al. Metabolomics and mitochondrial dysfunction in Alzheimer’s disease. Genes Genom 39, 295–300 (2017). https://doi.org/10.1007/s13258-016-0494-3

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    • DOI: https://doi.org/10.1007/s13258-016-0494-3

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