Part of the tragedy of Alzheimer’s is that when brain cells die, they do not return—a situation that does not appear to be the case in age-related forgetfulness. Instead of experiencing a full death, the neurons in the dentate gyrus are “sick” and “are simply not communicating as well as they should,” Small says. The experiment provides evidence that when brain cells in the dentate gyrus go offline as a result of normal aging, they might be unlocked through reintroduction of RbAp48, which could “rescue some of the memory loss,” Small says.
Not everyone is convinced that Alzheimer’s and age-related memory decline are entirely separate afflictions. Samuel Gandy, associate director of Alzheimer’s research at The Mount Sinai Hospital in New York City, thinks there could still be merit to the idea that the forgetfulness of old age and Alzheimer’s are part of a degeneration spectrum. He points to a well-known study published in 2012 in Nature, where scientists in Iceland found that a mutation in a certain gene appeared to protect against both Alzheimer’s and age-related cognitive decline. (Scientific American is part of Nature Publishing Group.)
But although Kandel agrees there could be multiple factors contributing memory decline, he says that his study provides strong evidence that a decrease in RbAp48 is a major component, and occurs in all individuals, regardless of their risk for Alzheimer’s.
In addition to clarifying the distinction between Alzheimer’s and memory decline in old age, the Columbia study opens up new avenues to explore regarding treatment for age-related memory decline. Several studies in recent years have pointed to everything from red wine to mental exercises as possible preventive measures against declining cognitive function. Still unknown: why RbAp48 decreases with age and whether these treatments may prevent that loss. But by testing the impact of, say, mental exercise on how well the dentate gyrus functions, researchers may be able to pin down more precisely what works and what does not.
And according to Small, one remedy is already available. “We can ask, is there any intervention that improves the performance of the dentate gyrus? And in fact there is something that has an effect, and it is called physical exercise,” Small says.
There may also be potential to develop pharmaceutical or nutraceutical solutions that would boost production of RbAp48 in the dentate gyrus.
As for Kandel, who was born in 1929, “I feel some decrease in memory, but I stay intellectually engaged,” he says. “I try to do new things in order to protect my cognitive capabilities.”