Understanding the role of SORLA in Alzheimer’s disease

In Alzheimer’s disease the amyloid protein builds up to form clumps, that trigger damage the brain and the symptoms of the disease. One of the molecules that regulates how much amyloid builds up is called SORLA.

Scientists have found strong links between SORLA and Alzheimer’s disease risk in mice, however, not many studies have looked at human cells. This pilot project, led by Dr Evans at the University of Edinburgh, will fill this gap in our current understanding.

Among other things, SORLA acts as a cargo molecule. It takes amyloid proteins to part of the cell where they can be broken down. This means when there is less SORLA more amyloid builds up and causes damage to the brain.

Some people have a genetic mutation in the DNA that provides the instructions for a cell to make the SORLA protein, which increases their risk of developing Alzheimer’s disease.

Dr Evans will use stem cell techniques to generate nerve cells that will produce the clumps of amyloid protein that we see in Alzheimer’s disease. She will delete the genes that make SORLA in these cells and measure their survival rate. She will also look at changes in the structure and function of the cells and other indications of Alzheimer’s disease.

The next step of Dr Evan’s research will be to compare normal human nerve cells to nerve cells lacking SORLA and to nerve cells with extra SORLA. From these results, Dr Evans will be able to describe how levels of SORLA increase someone’s risk of developing Alzheimer’s disease.

In the future she hopes this research will allow scientists to test for drugs that target SORLA.