Why one man with a genetic predisposition for Alzheimer’s disease is defying the odds

John Yang:

Nearly 7 million Americans currently live with Alzheimer's, and by 2060, experts say that number could be as high as 14 million. Scientists are trying to find out why one man has been able to stave off Alzheimer's for nearly 25 years despite having a rare genetic mutation that doctors say essentially guaranteed he developed the disease by his late 40s or early 50s. Ali Rogin spoke with Pam Belluck, health and science reporter for the New York Times.

Ali Rogin:

Pam, welcome back to the program. Who is this one man and why has he proven to be so essential to Alzheimer's research?

Pam Belluck, The New York Times:

So Doug Whitney is a 76-year-old who lives near Seattle, and he comes from a family where a lot of members of the family have inherited a rare genetic mutation. And the reason why Doug Whitney is so important is that he also has the mutation, but he has not developed Alzheimer's. And he is about 25 years past the age where it would have been expected for him to do so.

So scientists at Washington University School of medicine in St. Louis who study people with these rare mutations, they have been following him for 14 years, doing all kinds of tests on him, trying to figure out what's his, you know, biological secret sauce that is protecting him.

Ali Rogin:

And what have they found out so far? You mentioned they've been studying him. They've been running all kinds of tests. They've gone down some avenues. What has become clear so far?

Pam Belluck:

The interesting thing about him is that Alzheimer's disease, not only the rare kind, but the kind that, you know, is much more widespread, has sort of two proteins that are hallmarks of the disease. One is called amyloid. That's the protein that clumps into plaques in brains of people with Alzheimer's, usually forms about 20 years before symptoms emerge. And the second protein is called Tau. And that's the thing that forms these kind of sticky tangles. And that's much more connected to kind of symptoms of cognitive decline.

So what they've learned about Doug Whitney is that he has a whole lot of amyloid in his brain. He has amyloid levels that should suggest that he would have Alzheimer's many years ago even, but he has very little tau. So something in his biology has interrupted that progression from amyloid protein to tau protein. And that's what they want to zero in on.

They have discovered some clues. They don't have the exact answer. They haven't found, you know, the Eureka moment yet. But one of the most interesting things that they found is that he has a very high level of a different kind of protein called a heat shock protein. And these are proteins that, as the name, you know, suggests, they form in response to exposure to high heat. And they serve a purpose of keeping other kinds of proteins that tend to sort of go out of whack in neurological disorders in the right formation, Doug Whitney has a whole lot of heat shock proteins.

Why? One reason might be that for about a decade he was in the Navy, working in the engine room of a steam powered ship for many, many hours a day and exposed to such high heat that, you know, he had to be hosed down daily. And they think that may have driven his accumulation of these heat shock proteins. And if that's protecting him, that would be really instructive.

Ali Rogin:

And so then how are scientists looking to translate what they've learned about this kind of superhuman, yet everyday guy into broader, you know, progress in the field of Alzheimer's research?

Pam Belluck:

Right. So first they're trying to learn more about, you know, what else might be going on in his biology. So they're going to be looking at, you know, if you — are there other people with lots of heat shock proteins that also have delayed Alzheimer's. Can you recreate these kinds of effects in a lab, you know, in cells, in animals? Can you figure out what exactly is the thing that's cutting off the progression from those amyloid proteins to the tau proteins?

If they do that would really be huge because it could help inform the development of treatments that could do exactly that long before people develop symptoms of dementia. We only have very few drugs for Alzheimer's and they all work on a certain path. They all knock down your amyloid.

But so far they've been shown to only do a little bit, maybe slow down the disease progression for a relatively short amount of time.

So if we can find a way to say, you know what, amyloid accumulation, we don't need to worry so much about that. But what we really need to do is cut it off before it spreads into a tau accumulation and they can figure out a drug to do that would be a tremendous achievement.

Ali Rogin:

Pam Belluck with the New York Times, thank you so much.

Pam Belluck:

Thank you.