Age-Related Memory Loss is Not Alzheimer’s

Jessica Gwinn
By Jessica GwinnAugust 29, 2013

A new study at Columbia University Medical Center (CUMC) links a deficiency of the protein RbAp48  in the brain to age-related memory loss, which has been found to be unrelated to Alzheimer’s disease.

Our life’s memories are our biggest link to our past and they give us a sense of hope and belonging in a chaotic world. As we age, our brains age, too, and we can lose our ability to remember. This can be very distressing and scary.

But it turns out forgetting where we parked the car or neglecting to take our medication on schedule isn’t an automatic sign of Alzheimer’s. In fact, a breakthrough scientific study shows that age-related memory loss is a syndrome in its own right.

The good news about age-related memory loss? It’s potentially reversible.

A Protein Deficiency in the Brain

The study, at Columbia University Medical Center, led by Nobel laureate Eric R. Kandel, MD, has found that deficiency of a protein called RbAp48 in the hippocampus is a significant contributor to age-related memory loss.

This section of the brain, called the dentate gyrus (DG), has long been suspected of being especially vulnerable to aging. But, important to note: it is an entirely different neural area than where Alzheimer’s begins to form.

To determine whether RbAp48 plays an active role in age-related memory loss, the researchers turned to mouse studies. “The first question was whether RbAp48is down-regulated in aged mice,” said lead author Elias Pavlopoulos, PhD, associate research scientist in neuroscience at CUMC. “And indeed, that turned out to be the case — there was a reduction of RbAp48 protein in the DG.”

Published yesterday under the title “A Molecular Mechanism for Age-Related Memory Loss: The Histone Binding Protein RbAp48” in the online edition of Science Translational Medicine, the study was conducted in postmortem humans and in mice.

It’s the first of its kind to offer up direct evidence that age-related memory loss differs from Alzheimer’s disease. “Until now….no one has been able to identify specific molecular defects involved in age-related memory loss in humans,” said co-senior author Scott A. Small, MD, the Boris and Rose Katz Professor of Neurology and director of the Alzheimer’s Research Center at CUMC.

Why it’s Encouraging

About 40% of Americans age 85 and older say they experience some memory loss, a 2009 survey by the Pew Research Center found, as did 27 percent of those 75 to 84 and 20 percent of those ages 65 to 74.

Just knowing that there may be another reason — other than Alzheimer’s — as the cause for their age-related memory loss might set some people at ease.

In one of the experiments, the researchers used viral gene transfer and increased RbAp48expression in the DG of aged mice. “We were astonished that not only did this improve the mice’s performance on the memory tests, but their performance was comparable to that of young mice,” said Dr. Pavlopoulos.

“The fact that we were able to reverse age-related memory loss in mice is very encouraging,” said Dr. Kandel. “Of course, it’s possible that other changes in the DG contribute to this form of memory loss. But at the very least, it shows that this protein is a major factor, and it speaks to the fact that age-related memory loss is due to a functional change in neurons of some sort. Unlike with Alzheimer’s, there is no significant loss of neurons.”

A Look at the Future

Likely, scientists will conduct numerous clinical trials for the development of new drugs to treat this specific deficiency in the hippocampus. But that could take years.

‘As we want to live longer and stay engaged in a cognitively complex world, I think even mild age-related memory decline is meaningful,’ said Columbia neurologist Dr. Scott Small, a senior author of the study. ‘It opens up a whole avenue of investigation to now try to identify interventions.’

What This Means for You

For now, keeping your brain active and staying in good physical health is your best bet. And get out there and get some exercise.

As Small points out exercise makes the “dentate gyrus — that age-targeted spot in the hippocampus — function better,” Small said. He’s also studying if nutrition might make a difference. And, as for keeping your brain health, keep it simple. Small comments, “Just keep it up.” Socialization and brain stimulation –such as crossword puzzles, reading and other engaging activities — do wonders to exercise the brain and keep it healthy.

Jessica Gwinn

Jessica Gwinn

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