Susceptible brains
It has been suggested that Shakespeare’s King Lear’s serious mental deterioration is a dramatic study of dementia. The progressive confusion of the mind we call dementia affects 820,000 people in the UK. The name comes from the German psychiatrist, Alois Alzheimer, who first described it in 1906.

For the past 12 years, Professor Julie Williams and her team from the School of Medicine at the University of Cardiff have coordinated a project to identify susceptibility genes for Alzheimer’s disease, the most common cause of dementia. They have brought together research groups from several countries, including DNA samples from 25,000 individuals with Alzheimer’s disease and 45,000 without the disease. The ten genes, so far identified, reveal three ways in which the brain is susceptible.

Different reactions
The first difference is the inflammatory response of the brain. Professor Williams explains, ‘Alzheimer himself observed brain tissue that was a marker of the immune response in those brains. We thought this was a normal reaction to things going wrong in the brain, but these genetic findings are telling us that there is something different about the brain’s response and this is actually feeding into developing the disease.’

The second difference, says Professor Williams, is the genes affecting the way ‘the brain processes lipids associated with cholesterol. Cholesterol is an important molecule of the brain, for healthy nerve cells to survive and be active. Again, there appears to be something different about the way the brains of people with Alzheimer’s disease are processing these lipids.’

The third difference, Professor Williams describes, ‘is four genes, we have identified, that seem to affect a very specific cellular process called Endocytosis. This controls how big molecules get into and out of cells and how they are processed within those cells. There can be a number of ways that this could go wrong and is a process that we haven’t really prioritised yet in understanding the causes of Alzheimer’s disease.’