Amyloid β 1-42 induces hypometabolism in human stem cell-derived neuron and astrocyte networks


Alzheimer's disease (AD) is the most common form of dementia, affecting more than 35 million people worldwide. Brain hypometabolism is a major feature of AD, appearing decades before cognitive decline and pathologic lesions. To date, the majority of studies on hypometabolism in AD have used transgenic animal models or imaging studies of the human brain. As it is almost impossible to validate these findings using human tissue, alternative models are required. In this study, we show that human stem cell-derived neuron and astrocyte cultures treated with oligomers of amyloid beta 1-42 (Aβ1-42) also display a clear hypometabolism, particularly with regard to utilization of substrates such as glucose, pyruvate, lactate, and glutamate. In addition, a significant increase in the glycogen content of cells was also observed. These changes were accompanied by changes in NAD+ /NADH, ATP, and glutathione levels, suggesting a disruption in the energy-redox axis within these cultures. The high energy demands associated with neuronal functions such as memory formation and protection from oxidative stress put these cells at particular risk from Aβ-induced hypometabolism. Further research using this model may elucidate the mechanisms associated with Aβ-induced hypometabolism.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit Funding: Alzheimer's Research UK (PPG2009B-3). Supplementary available on the journal website.
Uncontrolled Keywords: Alzheimer's disease,amyloid,astrocytes,metabolism,neurons,stem cells,Cardiology and Cardiovascular Medicine,Clinical Neurology,Neurology
Publication ISSN: 1559-7016
Last Modified: 22 Apr 2024 07:11
Date Deposited: 19 Aug 2019 09:45
Full Text Link: http://www.natu ... bfm201558a.html
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2015-08-01
Published Online Date: 2015-04-08
Authors: Tarczyluk, Marta A.
Nagel, David A. (ORCID Profile 0000-0002-9055-1775)
Parri, H. Rhein (ORCID Profile 0000-0002-1412-2688)
Tse, Erin H.Y.
Brown, James E. (ORCID Profile 0000-0002-3504-7373)
Coleman, Michael D. (ORCID Profile 0000-0002-5510-6852)
Hill, Eric J. (ORCID Profile 0000-0002-9419-1500)



Version: Published Version

License: Creative Commons Attribution

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