Sunday, 07 June 2020 21:36

New human-on-a-chip system for Alzheimer research Featured

Scientists from Hesperos Inc., the University of Central Florida as well as from Michigan State University have developed a new human-on-a-chip system with which they have successfully investigated physiological effects of certain molecular forms of β amyloid proteins.


Basic research on Alzheimer's disease and drug development is mostly carried out on transgenic animal models. However, compounds that have been identified as safe and effective in animals have not led to an effective drug for humans. Therefore, hope is being placed on new methods that do not involve animal experiments. The scientists led by Prof. James J. Hickman, chief Scientist at Hesperos and Professor at the University of Central Florida, have developed a new in vitro model.  It consists of cortical neurons, co-cultured with human astrocytes on microelectrode arrays. The cells have been developed from human induced pluripotent stem cells (hiPSC).

The aim was to investigate the effects of amyloid-β and tau oligomers on the physiology and structure of neurons.

Two different protein deposits are found in Alzheimer patients: β-Amyloid-(Aβ) plaques and Tau fibrils. Although the protein deposits in the brain are typical for Alzheimer's disease, the Aβ proteins occur in different forms. They are present as monomers, but can also aggregate into several (oligomers) and finally into fibrils or plaques. Each of these different forms such as monomers, oligomers and plaques has different properties. Which form is ultimately responsible for neurodegeneration has not yet been conclusively clarified.

The researchers treated their cell culture with soluble Aβ oligomers and tau oligomers. In order to show that animal experiments do not yield additional knowledge, extracts from the brain of AD-transgenic mice from earlier studies were also used. It was examined whether the molecules lead to changes in the neurons developed from iPSC without causing the death of the cells.

The scientists were able to show that the treatment with oligomers led to disturbing information processing in the nerve cells within a short time, which could be measured on microelectrode arrays. In addition, the researchers used patch-clamp measurements to determine the dysfunctional electrical properties of the nerve cells as well as morphological alterations in the length of axons and branching. However, the viability of the cells was not affected.

The results confirm the suitability of the model to reproduce important aspects of Alzheimer's pathology, in particular disturbances in long-term
potentiation (LTP)  (1) and is suitable as a platform for drug development for the early stages of Alzheimer's disease.

The scientists initially plan to conduct further studies with known therapeutics to improve the symptoms of Alzheimer's disease.

Original publication:
Caneus, J., Akanda, N., Rumsey, J. W., Guo, X., Jackson, M., Long, C. J., Sommerhage, F., Georgieva, S., Kanaan, N. M., Morgan, D., & Hickman, J. J. (2020). A human induced pluripotent stem cell-derived cortical neuron human-on-a chip system to study Aβ42 and tau-induced pathophysiological effects on long-term potentiation. Alzheimer's & dementia (New York, N. Y.), 6(1), e12029. https://doi.org/10.1002/trc2.12029

Source:
https://www.businesswire.com/news/home/20200529005128/en/Hesperos-Human-on-a-Chip%C2%AE-System-Model-Preclinical-Stages-Alzheimer%E2%80%99s

(1 ) Whitlock, J.R., Heynen, A.J., Shuler, M.G. & Bear, M.F. (2006). Learning induces long-term potentiation in the hippocampus. Science 313(5790): 1093-1097. doi:10.1126/science.1128134