We’re all at risk now by virtue of the fact that we are part of an aging population. It’s clear that the biggest risk for Alzheimer’s disease is aging. That’s why we know so much about it now. In this century the population is aging more successfully than ever before.
Alzheimer’s wasn’t as prevalent because we weren’t living as long?
Yes. At the turn of the century the average age life expectancy for males in some European cities was only 40 or 50-years-old. Now it’s 20 or 30 years more than that. So we didn’t see the population coming into the age that put them at risk for developing the disease.
Talk about the vascular connection
The connection has been known for a long time, ever since Alzheimer described the disease. There’s a small protein called amyloid that gets deposited in the brains of those that suffer from Alzheimer’s disease. There’s always been a question of how it causes the disease and if it has any normal functions. We started to look into that problem several years ago. One of the things we found was that when amyloid comes anywhere near blood vessels, it causes them to constrict and stay constricted. That was a novel finding, and there are several implications. This might be part and parcel of the Alzheimer process, that there may be a tendency of the vessels in the brain to close down and stay closed down. Of course that would have implications for delivering oxygen and nutrients to the nerve cells in the brain.
So this connection happens years before the amyloid?
Yes. One of the interesting aspects of this is that in full-blown Alzheimer’s disease you have aggregations of amyloid that precipitate out. They come out of solution and form plaques in the brain. Our findings occur with much lower concentrations. So the implication is some of the affects that we’re looking at occur many years early on before the disease really becomes full-blown and recognized in the way that we see it clinically.
Would you be able to see the vessels closed on an MRI or something?
I wish we could, but it’s very difficult to do that in humans. We have done animal studies that show that. The animals that produce too much amyloid do close their vessels, and they stay closed. That gives them significant problems.
Is this the same as somebody who has cardiovascular disease? If they have cardiovascular problems, would they be at a higher risk for Alzheimer’s?
If you have a little bit of Alzheimer’s and you have a little bit of cerebral vascular disease or even cardiovascular disease, those things can combine in a way that makes them both work. You can see individuals that have a slight amount of Alzheimer’s disease pathology and normally wouldn’t have any symptoms. If they have cerebral vascular problems on top of that, then they start to display symptoms.
People might see that and say, “If I had a heart attack, then I might be an Alzheimer’s patient later on.” Is that true?
If you have a heart attack then you usually have some form of atherosclerosis or some form of vascular disease. Quite often it extends to elsewhere in the body. Yes, that does put you at risk for increasing the expression of Alzheimer’s disease. In other words, it does put you at risk for having Alzheimer’s symptoms before you normally would if you just had Alzheimer’s alone.
Now that you understand this connection, where do you go from here?
What we’ve been working on for the last couple of years is finding out exactly why the vessels close down. To start with, we thought that it was mediated by free radicals. These substances increase with age and are generally thought to be bad news in a number of conditions. However, what we actually found out is the vessels close down because they began an inflammatory response. It’s the same as when you first scratch yourself the skin blotch is white because there’s an immediate inflammatory response. In fact, the blood vessels in the brain are doing something very similar when they come into contact with amyloid.
How would you treat this?
If we block the actual molecular mechanisms, the chemicals that are switched on inside cells, we can stop the effect. We’ve already demonstrated that in the experimental situation. Now what we have to do is demonstrate that in the clinic. That’s the next step.
Could drugs used for cardiovascular disease be used?
Yes. One of the first drugs we’ve investigated that blocks this effect in the experimental situation has been used for other conditions. It’s never been used for Alzheimer’s disease, but it has been used for cardiovascular disease. It’s that kind of drug that we want to test in a clinical situation.
What are those drugs?
We don’t have the full FDA approval to say.
Do antioxidants help?
As far as the vessel discovery is concerned, antioxidants mop up free radicals, and free radicals seem to make the situation much worse. That was one of the first things we found. So we’re not pursuing that in the clinic.
Using the cardiovascular connection as an identifier, it could be years before we see Alzheimer’s. How do you treat current Alzheimer’s patients if it’s already beyond that?
One of the other groups of patients that we look at are people that don’t have Alzheimer’s disease but are before that stage. They are memory-impaired but don’t have full-blown Alzheimer’s disease. If we follow a group like that, then we know that a certain percentage, quite a high percentage convert to Alzheimer’s disease every year. They would be an ideal population for us to give this medication to. That would be a much better intervention than waiting until folks have full-blown disease. That group is a target population for us.
So people who already have it might not benefit from this?
It’s generally recognized that once you’ve had the disease for five or six years then there’s very little that medical intervention can do now. The real target populations are those folks that are in the very early stages of Alzheimer’s disease or who would develop Alzheimer’s disease in the next several years. Right now those are the groups that we are actively recruiting into our study.
How do you identify those people?
We have sophisticated memory screens that give evaluations. These evaluations look at every aspect of memory and distinguish those effects that are truly pathological from those that are simple forgetfulness, which we all suffer from in one form or another.
Will you identify whether or not the amyloid is present?
We can’t detect amyloid in the brain. There’s no known way for us to do that at this stage. What we have to do is identify individuals who have memory impairment but don’t have full-blown Alzheimer’s disease and recruit those into our studies knowing that the largest majority of those will in fact develop the disease over a four- or five-year-period.
If I know somebody in my family who has it, what are my chances of developing Alzheimer’s?
One’s risk for the disease is definitely increased if you have a family history. However, the reality of that statement is it’s such a prevalent disorder, if most of us look far enough into our family histories we’ll find a case of Alzheimer’s disease. That’s just another way of saying that as we get to be 80 or 90 we’re all at risk for the disease. However, if you have a strong family history in addition to age, your risk is increased still further.
Are men or women more at risk?
Men and women are equally at risk for the disease. Men tend to die from other things before they get Alzheimer’s disease. So there’s an imbalance in the absolute numbers in the population. If you just take 100 women and 100 men, they’re equally at risk for the disease as they age.
News Source: Ivanhoe Newswire – 1999