A Single Protein May Help Explain Memory Loss In Old Age

Aug 29, 2013
Originally published on August 30, 2013 2:26 pm

If you're finding it harder to remember where you put the car keys, the culprit could be a brain protein with a name that's easy to forget: RbAp48.

A shortage of this protein appears to impair our ability to remember things as we age, researchers report in the current issue of Science Translational Medicine. And boosting levels of RbAP48 in aging brains can reverse memory loss, at least in mice, they say.

The protein was studied in an area of the brain that is generally unaffected by Alzheimer's disease. The research "reinforces the emerging idea that Alzheimer's disease and aging are separate entities," says Scott Small, a neurologist at Columbia University and one of the study's authors. It also suggests that, eventually, it should be possible to treat memory loss that's not related to Alzheimer's.

Small and a team that included Nobel Laureate Eric Kandel discovered the protein after studying postmortem brains from eight people ranging in age from 33 to 88. The scientists focused on one specific region of the hippocampus, a structure that's highly involved in memory.

"We simply asked: Can we find a molecular change in that brain region across the lifespan?" Small says. The answer was yes. In the brains of young people, the RbAp48 protein was abundant, the researchers report. But in older people it was scarce.

The team still needed to show that this protein really is responsible for memory loss. So they found a way to artificially reduce levels in young mice, Small says.

"What was remarkable is that if you just manipulate this one molecule in this particular area of the brain, you now have a young mouse that looks very much like an old mouse," Small says. These young mice had trouble remembering new objects and things like how to get through a maze.

Then the researchers tried something even more ambitious. They boosted levels of RbAp48 in old mice with failing memories. The effect was dramatic, Small says. "Their ability to detect novel objects went back to the way a young mouse is able to perform that task," he says.

All of these experiments involved what's called the dentate gyrus — a region of the hippocampus that is generally not affected by Alzheimer's disease. Also, the RbAp48 protein hasn't been linked to Alzheimer's, Small says.

The findings could eventually help doctors determine whether someone's memory loss is a symptom of early Alzheimer's or just normal aging, Small says. "That's become the most common question I get" from patients, he says.

The new study is both beautiful and important, says David Sweatt a neurobiologist at the University of Alabama at Birmingham School of Medicine. The findings suggest that a drug could reverse memory loss in some people with age-related memory loss, Sweatt says.

But the possibility of finding such a drug raises a tricky question for society. "If it's normal, do you need a drug for it?" Sweatt says.

Sweatt thinks there is a need because even normal memory loss impairs the lives of many people in their 70s, 80s and beyond. But a drug isn't the only option for increasing levels of this memory molecule, he says. Other likely candidates include diet and exercise, which scientists already know can affect the levels of some proteins in the brain.

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Transcript

MELISSA BLOCK, HOST:

From NPR News, this is ALL THINGS CONSIDERED. I'm Melissa Block.

ROBERT SIEGEL, HOST:

And I'm Robert Siegel.

Now some good news for those of us who don't remember things quite so well as we used to. New research indicates that many age-related memory problems have nothing to do with Alzheimer's disease.

And NPR's Jon Hamilton reports that, at least in mice, some of these memory problems can be reversed.

JON HAMIILTON, BYLINE: When older people begin to suspect that their memory is getting worse, they often visit a neurologist - someone like Scott Small at Columbia University. Small says these people tend to have a common list of complaints.

SCOTT SMALL: Forgetting where things are placed, not being able to remember things as well as one used to. And I think an important part of this is that that's exactly the way the earliest stages of Alzheimer's can present, as well.

HAMIILTON: Small says his patients usually want to know whether they have Alzheimer's or just the normal memory problems that come with age.

SMALL: That's become the most common question I get. And that's exactly what the field at large is trying to address.

HAMIILTON: Right now, though, there's still no way to tell early Alzheimer's from age-related memory loss. So, Small and a team of researchers decided to look for something that might be causing memory problems in healthy brains as they get older. They began by studying post-mortem brains from eight people of various ages. Small says they focused on one region of the hippocampus, the structure that's highly involved in memory.

SMALL: And we simply asked, can we find a molecular change in that brain region across the lifespan.

HAMIILTON: The answer, reported in the journal Science Translational Medicine, was yes. As people got older, levels of one particular molecule declined dramatically. It's a molecule that helps DNA in the brain make important proteins. But the team still needed to show that this molecule really was responsible for memory loss. So, Small says they found a way to artificially reduce levels in young mice.

SMALL: What was remarkable is that if you just manipulate this one molecule in this particular area of the brain, you now have a young mouse that looks very much like an old mouse.

HAMIILTON: The young mice had trouble remembering new objects and things like how to get through a maze. Then the researchers tried something even more ambitious. They boosted levels of the memory molecule in old mice with failing memories. Small says the effect was dramatic.

SMALL: They remarkably looked very similar to young mice. Their ability to detect novel objects went back to the way a young mouse is able to perform that task.

HAMIILTON: All of these experiments involved a region of the hippocampus that's generally not affected by Alzheimer's disease. Small says the molecule being manipulated also is not known to be associated with Alzheimer's.

SMALL: This reinforces the emerging idea that Alzheimer's disease and aging are separate entities. They both cause memory loss through different mechanisms.

HAMIILTON: Small says the finding could eventually help doctors quickly determine whether a patient's memory loss is being caused by Alzheimer's or something else.

David Sweatt, of the University of Alabama at Birmingham, calls the new research beautiful and important. He says it will take more studies to definitively show that there's no link between Alzheimer's and normal aging. But in the meantime, he says, the findings suggest that it could be possible to reverse memory loss in some people.

DAVID SWEATT: One of the most exciting aspects of these studies is that you could use this protein as a potential target for developing therapies, for age-related memory decline.

HAMIILTON: Sweatt says this new possibility of creating a drug to improve memory raises a tricky question for society.

SWEATT: Whether something that we would characterize as a normal age-related process, is that something that we should consider as being amenable to drug development. That is, if it's normal, do you need a drug for it?

HAMIILTON: Sweatt says he thinks a drug like that is worth developing because it could improve the lives of many people in their 70's, 80's and beyond. But he also says drugs may just be one way to increase levels of this memory molecule. Other likely candidates include diet and exercise, which scientists already know can affect the levels of some proteins in the brain.

Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.