The scientists used skin cells donated from healthy volunteers and those with Down’s syndrome and turned them into stem cells. These stem cells were then used to generate networks of functioning nerve cells in the lab, which resemble the complex wiring of cells in the human cerebral cortex. The cortex, which makes up over three quarters of the brain, houses many of the nerve cells involved in memory and thinking and suffers particular damage during Alzheimer’s.
People with Down’s syndrome have an extra copy of chromosome 21, a segment of DNA that carries a gene responsible for producing the Alzheimer’s protein amyloid. Due to this extra version of the gene, people with Down’s syndrome have a much higher incidence of Alzheimer’s than the rest of the population. By generating nerve cells from skin cells of people with Down’s syndrome, the scientists could observe the disease process over a period of weeks and compare this to those cells derived from healthy volunteers.
Dr Rick Livesey, who led the study at the Wellcome Trust and Cancer Research UK Gurdon Institute at the University of Cambridge, said: “One of the biggest challenges facing dementia researchers at the moment is a lack of good ways to track the disease over time. By using stem cells donated from people with Down’s syndrome – who are much more likely to develop Alzheimer’s – we have been able to track how the disease develops over a shorter time period than has been possible in the past.”
Within 28 days, the nerve cells made from people with Down’s syndrome showed more than double the amount of the Alzheimer’s protein amyloid than those from healthy volunteers and this built up into amyloid plaques within two months. The scientists also observed that a protein called tau became abnormally altered and distributed in the cells- one of the common later-stage characteristics of the disease.
Dr Livesey added: “What is promising about this stem cell technique is that we can create functioning human cortex cells in a dish, allowing us to more closely model what is happening in our brains. Not only this, but our new model shows many of the characteristic features of human Alzheimer’s disease and will allow us to test new treatments more easily.”
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, welcomed the findings. He said: “We are pleased to have contributed funding towards this study and we hope it can be used to unravel some of the remaining questions about how Alzheimer’s progresses.
Modelling a complex disease like Alzheimer’s is a big challenge, but innovative approaches like this can improve our understanding. As the stem cells in this study were donated by people with Down’s syndrome, they differ genetically to the rest of the population, but could still offer valuable insight into the disease processes in Alzheimer’s.
“Increasing our understanding of dementia is essential not only for people with Down’s syndrome, but for the 820,000 people across the UK living with the condition. It is essential that we improve the models that we have for understanding dementia, but this can only be done through research. As dementia research is so desperately underfunded, we must invest now if we are to find the answers that are so urgently needed.”
from the University of Cambridge