The Genetics of Alzheimers

Helen - Now, Alzheimer's disease is the most common form of dementia, mostly in the elderly, and a great deal of research is underway to understand, treat, and try and prevent Alzheimer's. But there are currently no effective treatments for it. Now Professor Julie Williams and her team at Cardiff University recently discovered a pair of genes that seem to be link to Alzheimer's. And she joins us now. Hello, Julie.

Julie - Hello, Helen.

Helen - Thanks for coming along on the show. First of all, just what causes Alzheimer's?

Julie - Well, Alzheimer's is caused by genetic and non-genetic factors. We know that there are three genes already that contribute to and cause rare forms of Alzheimer's disease and one gene that increases risk of developing the common form of Alzheimer's disease. And that's the position we were at before we publish our research.

Helen - And do we know what's going on inside the brain when people have Alzheimer's? What's the problem there?

Julie - Well, we know there are certain markers of the disease. So, you see in the brains of Alzheimer's cases, plaques that are made up of what we call beta-amyloid mainly and these occur outside the dying brain cells. Within these brain cells that are dying, you see tangles made up of microtubules. So those are the two markers there. But what exactly is going on is still a basic mystery for us.

Helen - So we have these plaques of beta-amyloid and that's a type of protein, isn't it?

Julie - Yes.

Helen - Yes and do we have any idea now, how these genes now might be involved in those markers, those plaques that we're finding in the brains of people with Alzheimer's?

Julie - Okay. The rare forms, the forms that are contributed to by single gene defects, these occur in genes known as APP and the pre-sinilins, these we know affect the amount of beta-amyloid that occurs in the brain. But what we don't know is, is that the same process for those with the more common form of Alzheimer's disease? And our results will actually tend to support a different, slightly different, process involved in common Alzheimer's disease compared to the rare forms that we've known about for some years.

Helen - So what do we think is going on in that common form of Alzheimer's?

Julie - Okay. What our research has shown is that we identified two new genes that increased risk of developing common Alzheimer's disease. The genes are clusterin and PICALM. And when we put our data are studied together with a French study. We now have definitely three new genes and an additional fourth new gene. And this is opening up new ideas about what actually causes the more common form of Alzheimer's disease.

Helen - And how did you find that association? Did you go out and look at people who got Alzheimer's and look at the genes they have and compar that amongst the population and discover these, sort of, unique genes that might lead to the condition?

Julie - That was exactly right. But it was quite a large experiment and we looked at the genes of 4,000 individuals with Alzheimer's disease and compared over half a million individual variations in each of those individuals, and compared those to 8,000 individuals without Alzheimer's disease. So this is the biggest study of its type, currently published.

Helen - And do we have any idea what these genes normally do and what might be going wrong in the people who got Alzheimer's?

Julie - Okay, some of these genes are involved in a theme that's developing in this program of inflammation which surprised us to some extent. So, the compliment receptor gene, clusterin, is involved in protecting the brain through the inflammatory response, the classical compliment system. And what this is telling us is that inflammation is a primary event in the disease production. We had known for a number of years that you see markers of inflammation within the brains of Alzheimer's individuals. We thought this was secondary to the amyloid plaques for example. But this appears now to be a primary element in disease production. The other element is cholesterol. We see a lot more genes involved in cholesterol and sterol, and we really don't what they are doing but we do know that they are playing a crucial role in disease development.