Monday 04 January 2010

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Health Report 28 min 1 speaker 8 chapters transcribed 3 days ago

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What is the link between sugar metabolism and Alzheimer’s disease?

Norman Swann 0:00

Hello and welcome to the Health Report with me, Norman Swan. Today, what does it take to be a super-aged, super-thinker, having a mind in your 90s that's as good or better than people decades younger? Research is coming up with some answers on this, plus a lot more on keeping our minds in order as we age. For example, research in Chicago is suggesting that sugar might have something to do with Alzheimer's. The sugar story is linked to a destructive chemical that's thought to lie at the heart of this form of dementia. It's called beta-amyloid. Professor Bob Vassar is at Northwestern University School of Medicine.

Bob Vassar 0:37

There was an observation that's now about 25 years old that patients with Alzheimer's disease have a problem with using the sugar glucose. Now, glucose is the primary fuel that the brain uses for energy. The brain is probably the highest user of glucose in the body, isn't it? Yes, it is a very, very high glucose user. Actually, patients with Alzheimer's disease use less glucose in their brains. Some scientists believe it's because those brain cells are dying and therefore dead neurons, dead brain cells don't use glucose. But I started looking at it the other way. Perhaps there's a problem with blood flow in the brain and it's actually the delivery of glucose to those brain cells that might be the problem.

Bob Vassar 1:19

And then you discovered this enzyme, which originally was a different part of the story. Yes. We did know that the beta amyloid was likely to be a cause of Alzheimer's disease. But there were enzymes that would produce this beta amyloid.

Norman Swann 1:34

And we should just say here what an enzyme is because it's thrown around a lot. You know, you buy it in your washing powder.

Bob Vassar 1:38

We talk

Norman Swann 1:38

about enzymes all the time. But these are chemicals that help a chemical reaction to go along without changing themselves. They're a helper to make things go better.

Bob Vassar 1:47

Yes. Ten years ago this year, we discovered the enzyme that is a key producer of the beta amyloid in the brain. So beta amyloid needs this enzyme to be produced. Exactly. And this enzyme is called BACE, B-A-C-E. And it's actually a very attractive drug target for Alzheimer's disease because if you could block this base enzyme with a drug, then you would prevent the formation of the toxic beta amyloid. And that should be a good thing for Alzheimer's. So people with Alzheimer's disease have high levels of this enzyme? Yes, they do. Actually, that was our work as well as work from other labs. So the next question became is... Why? Why is the base enzyme going up? And that's where this story about glucose in the brain comes in.

Bob Vassar 2:31

So I mentioned earlier that it was observed that the glucose utilization in the brains of Alzheimer's patients is low compared to normal people.

How does the enzyme BACE influence beta‑amyloid production?

Bob Vassar 2:40

And we wanted to investigate if reduced glucose in the brain might be causing the base enzyme to go up, which would in turn make the beta amyloid production go up. And so we used a couple different genetically engineered mouse models of Alzheimer's disease, and these mice developed the amyloid plaques, similar to what humans develop in Alzheimer's disease. And we treated these mice with drugs that would block their utilization of glucose in the brain. And lo and behold, we did see that the base enzyme levels went up, and that in turn caused the beta amyloid levels to go up. So

Norman Swann 3:19

what's going on here? I mean, if you've got poor glucose uptake, I mean, if you were looking at muscles and you were looking at an elderly person and they weren't picking up glucose into their muscle, you'd say, well, they've got prediabetes or type 2 diabetes. They're insulin resistant and they're the glucose isn't getting across into

Bob Vassar 3:34

the

Norman Swann 3:34

cell. So is that what you're seeing inside the brain that in fact they've got a brain form of type 2 diabetes or insulin resistance? What do you think is going on here?

Bob Vassar 3:44

That's an interesting hypothesis and there are several scientists I know that are interested in that and they're pursuing that as a possibility. I favor the concept that during aging there's a chronic problem that begins to occur with the cardiovascular system