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

Marta A. Tarczyluk, David A. Nagel, H. Rhein Parri, Erin H.Y. Tse, James E. Brown, Michael D. Coleman, Eric J. Hill*

*Corresponding author for this work

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)1348-1357
Number of pages10
JournalJournal of Cerebral Bood Fow and Metabolism
Issue number8
Early online date8 Apr 2015
Publication statusPublished - 1 Aug 2015

Bibliographical note

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Funding: Alzheimer's Research UK (PPG2009B-3).

Supplementary available on the journal website.


  • Alzheimer's disease
  • amyloid
  • astrocytes
  • metabolism
  • neurons
  • stem cells

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  • Research Output

    The development of functional astrocyte-neuron networks derived from stem cells

    Hill, E. J., 2015.

    Research output: Contribution to conferenceAbstract

    Open Access
  • Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network

    Tarczyluk, M. A., Nagel, D. A., O'Neil, J., Parri, H. R., Tse, E. H. Y., Coleman, M. D. & Hill, E. J., Sep 2013, In : Journal of Cerebral Bood Fow and Metabolism. 33, 9, p. 1386-1393 8 p.

    Research output: Contribution to journalArticle

    Open Access
  • NT2 derived neuronal and astrocytic network signalling

    Hill, E., Jiménez-González, M., Tarczyluk, M., Nagel, D. A., Coleman, M. D. & Parri, R., 2 May 2012, In : PLoS ONE. 7, 5, 10 p., e36098.

    Research output: Contribution to journalArticle

    Open Access
  • Student Theses

    Aβ(1-42) induced metabolic effects in a stem cell derived neuron and astrocyte network.

    Author: Tarczyluk, M., 30 Jul 2013

    Supervisor: Parri, H. R. (Supervisor) & Hill, E. J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy


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