Discussion

Alzheimer’s Disease (AD) is the most common form of dementia, affecting more than 35 million people worldwide. Currently the majority of studies on AD have used transgenic animal models or imaging studies of the human brain. It is almost impossible to validate these findings using human tissue. Whilst animal models have been central to our understanding of human physiology, human stem cell based models may help us to further our understanding of human physiology tackle devastating diseases such as Alzheimer’s disease. Brain hypometabolism is a major feature of AD, appearing decades before cognitive decline and pathological lesions. In this study we demonstrate that human stem cell-derived neuron and astrocyte cultures treated with oligomers of amyloid beta display a clear hypometabolism, particularly with regards to utilisation of substrates such as glucose, pyruvate, lactate and glutamate. As many neuronal functions, such as memory formation and protection from oxidative stress require energy formed from oxidative phosphorylation these cell are at high risk from hypometabolism. Further research using models derived from iPSCs may elucidate the mechanisms associated with Aβ induced hypometabolism and therefore expedite the discovery of novel biomarkers as well as mechanisms associated with disease progression.