Monthly Archives: February 2012

Scientists in the US have used stem cells from patients to overcome the challenge of obtaining live brain cells, allowing them to learn more about the causes of Alzheimer’s. The study, published online today in the journal Nature, provides new opportunities for scientists to model the complex disease.

Induced pluripotent stem cells, or iPSCs, are cells which have been taken from one part of the body and can be reprogrammed into other cell types. They allow scientists to overcome the challenge of obtaining live cells from the brain – as they can take skin cells from people and transform them into brain cells.

The scientists used iPSCs to investigate what goes wrong in brain cells of people with both late-onset Alzheimer’s, and those with familial Alzheimer’s – an inherited form which tends to affect people at a younger age. Skin cells (or fibroblasts) were obtained from two people with familial Alzheimer’s, two people with late-onset Alzheimer’s disease, and two people without dementia to act as controls. The fibroblast cells were transformed into brain nerve cells in the lab and the scientists looked for features of Alzheimer’s in these cells.

The study showed that nerve cells derived from the two volunteers with familial Alzheimer’s and one of those with late-onset Alzheimer’s produced high levels of amyloid and tau, two characteristic proteins involved in Alzheimer’s. They also produced high levels of a protein called active GSK-3β which can be responsible for turning tau into its more toxic form. They also found that one particular inhibitor of amyloid production could reduce the levels of all three proteins in these cells.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said:
“Induced pluripotent stem cells have the potential to provide a great resource for scientists to study diseases such as Alzheimer’s – where getting access to human brain cells to study is a huge challenge. The authors have shown that these cells can reveal vital clues about the biological changes taking place during Alzheimer’s and we hope further studies can expand on these early findings.

“In light of the recent European ban on patents using human embryonic stem cells, it may prove important to increase our use of technology using these non-embryonic stem cells. We hope that studies like this one will drive scientific research forward and help us to understand the biology behind different forms of Alzheimer’s and test new treatments. With 820,000 in the UK living with dementia, the need for such research has never been greater.”

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Scientists at the University of Cambridge have developed a new and innovative way to study Alzheimer’s disease in the lab. The stem cell technique, which allows researchers to track the disease over a matter of weeks, could provide a valuable tool for scientists to unravel the complexity of Alzheimer’s and test potential new treatments. The findings, funded by Alzheimer’s Research UK and the Wellcome Trust, will be published today in the journal Science Translational Medicine.

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.”

For further information, or to speak with Dr Rick Livesey or Dr Simon Ridley, please contact Laura Phipps, Science Communications Officer at Alzheimer’s Research UK on 01223 843304, mobile 07500 803936 or email press@alzheimersresearchuk.org  

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US scientists have found that men may be at higher risk than women of mild cognitive impairment – a stage that often precedes dementia. The study is published online in the journal Neurology.

Researchers from the Mayo Clinic in Rochester, Minnesota, studied 1,450 people between the ages of 70 and 89, for an average of three years. Participants took part in evaluations every 15 months to assess whether or not they had mild cognitive impairment (MCI). MCI causes problems with memory and other thinking skills, but not to an extent that interferes with everyday life. Roughly half of all people who are diagnosed with MCI go on to develop dementia, usually Alzheimer’s disease, within five years.

Over the course of the study, 296 people were diagnosed with MCI, but the researchers found that men were more likely to develop the condition than women. The results were surprising because previous research has shown women are more likely to develop dementia than men.

Further analysis showed that MCI with memory loss – known as amnestic MCI – was more common than non-amnestic MCI, where memory loss is not a major symptom. People who had less education or were not married were also more likely to develop MCI. The scientists suggest that further research could reveal whether different risk factors affect separate groups of people in different ways.

Dr Marie Janson, Director of Development at Alzheimer’s Research UK, said:
“These surprising results suggest that men may be at greater risk for MCI despite having a lower risk for dementia, and it will be important to see whether further studies can replicate these findings. A key goal for research is to identify why some people with MCI develop dementia while others don’t. If we can understand why some people have a greater risk for cognitive decline and dementia, we stand a better chance of being able to prevent the condition.

“With 820,000 people affected by dementia, and a rapidly ageing population, the need for research to find new ways to treat and prevent the condition has never been more urgent.”

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