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Glucose regulates amyloid β production via AMPK

  • Translational Neurosciences - Original Article
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Abstract

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.

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Acknowledgments

This study was supported by grants from Ministry of Science and Technology of Taiwan to YMK (101-2320-B-006-006-MY3) and TTY (102-2314-B-214-006-MY3). We thank Ms. Tiffany Hu for reading and commenting on the manuscript.

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Authors and Affiliations

  1. Department of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan

    Ting-Ting Yang & Yun-Wen Chen

  2. Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan

    Yao-Shan Shih, Yu-Min Kuo & Chu-Wan Lee

  3. Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan

    Yun-Wen Chen & Yu-Min Kuo

  4. Department of Nursing, National Tainan Institute of Nursing, Tainan, Taiwan

    Chu-Wan Lee

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  1. Ting-Ting Yang
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  2. Yao-Shan Shih
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  3. Yun-Wen Chen
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  4. Yu-Min Kuo
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Correspondence to Ting-Ting Yang or Chu-Wan Lee.

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Yang, TT., Shih, YS., Chen, YW. et al. Glucose regulates amyloid β production via AMPK. J Neural Transm 122, 1381–1390 (2015). https://doi.org/10.1007/s00702-015-1413-5

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