Investigating the brain’s protective cells

Lead Investigator: Dr Kaylene Young
Institution: The Menzies Institute, Australia & University College London
Grant type: Project
Start date: February 2011
Completed date: April 2014
Amount: £268,779

Scientific Title: Oligodendrocyte Progenitor Cells - A New Target for Alzheimer's Disease Treatment.

What was the project, and what did the researchers do?

This project was to investigate a type of 'support cell' within the brain called oligodendrocytes, working to understand how they are affected during Alzheimer's disease and whether this could provide an avenue for potential future treatments. 

Oligodendrocytes form the white matter of the brain, which forms a covering for the connections between nerve cells to make communication between cells faster and to protect them from damage. This is made of a fatty substance called myelin. A reduction in the amount of myelin is associated with worse functioning of nerve cells, also leaving them vulnerable to damage and death. 

This study focused on the effects on a type of stem cell within the brain called oligodendrocyte precursor cells. These can mature into fully functioning oligodendrocytes and the numbers being produced and reaching maturity is a good indicator of the health of that system.

What were the key results, and how will this help in the fight against dementia?

Mice with amyloid plaques, a hallmark of Alzheimer's disease, were found to have oligodendrocyte precursor cells and neural stem cells (stem cells that mature to form nerve cells, neurons) that divided more, so producing more stem cells and potentially more mature cells, in a process that was altered by signals from the protein that is broken down to form amyloid. 

Understanding what these signals are and how to alter them could be a way that cell production can be increased with a view to repairing damage caused during dementia.

Despite the increased rate of creation of these oligodendrocytes, the researchers found that their function was slightly impaired in mice of a certain age. The form of this impairment was unexpected, and more research is needed to fully understand implications for the development and progression of dementia.

However, the fact that these cells are still produced and this system is still functioning within brains undergoing changes associated with Alzheimer's disease is promising, as it opens up a new route for potential future therapies to slow or stop the progression of the disease.

What happened next? Future work and additional grants

In 2014 Kaylene Young was awarded a prize for outstanding work in the field of stem cell science; she was awarded the National Stem Cell Foundation of Australia's Metcalf Prize.

The researchers are continuing their research by investigating the effects of a drug that has been shown to increase the division of oligodendrocyte stem cells and so the number of mature oligodendrocytes produced.

How were people told about the results? Conferences and publications

Papers

Hu, Y et al (2013). Role of cystatin C in amyloid precursor protein‐induced proliferation of neural stem/progenitor cells. J Biol Chem. 288(26):18853‐62.

Young, K M et al (2013). Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodelling. Neuron 77, 873–885, 2013.

Clarke, L & Young, KM et al (2012). Properties and Fate of Oligodendrocyte Progenitor Cells in the Corpus Callosum, Motor Cortex and Piriform Cortex of the Mouse. J Neurosci. 32(24): 8173‐8185.

Richardson WD et al (2011). NG2‐glia as Multipotent Neural Stem Cells: Fact or Fantasy? Neuron. 70(4):661‐73.
Wang S and Young KM (2013). White Matter Plasticity in Adulthood. Neuroscience http://dx.doi.org/10.1016/j.neuroscience.2013.10.018

Small DH et al (2013). Beta‐Amyloid Precursor Protein: Function in Stem Cell Development and Alzheimer's Disease Brain. Neurodegener Dis. 13(2‐3):96‐8.

Conferences and dissemination

Kaylene Young. Stem Cells Short‐Circuit Nerve Diseases. Australasian Science Magazine, November 2013 Edition.

Michelle Paine. Alzheimer's Study Leap. The Mercury Newspaper, Saturday March 16th 2013. An interview with Dr Young about her research findings was also shown on Southern Cross Television News and live Australian Broadcasting Commission drive‐time radio.

Dr Young has given three public research seminars and visited two high schools in the last two years to talk about using neural stem cells and OPCs for brain repair and our goal to develop a treatment for Alzheimer's disease.

This project is jointly funded by Alzheimer's Society and the Bupa foundation