One common myth is that age-related memory loss is an early indication of Alzheimer’s disease. But researchers at the Columbia University Medical Center in New York City have found a specific protein, RbAp48, that they believe is responsible for age-related memory problems. What’s more, by replenishing RbAp48 in the brains of mice, the researchers were able to undo existing age-related memory damage.
The distinction between Alzheimer’s disease and age-related memory loss makes all the difference in getting to the root cause of each condition.
Just because your memory seems to be on the decline doesn't mean there isn't a way to turn back the clock, says lead study author Elias Pavlopoulos, Ph.D., an associate researcher in neuroscience at Columbia. “Our findings show that age-related memory decline might be ameliorated,” he says.
Rebooting Your Memory
“Despite the anatomical discrimination between age-related memory loss and Alzheimer’s disease, no one has been able to identify specific molecular defects involved in age-related memory loss in humans and...show that it is fundamentally different from Alzheimer’s,” Pavlopoulos says. That missing molecular link is RbAp48.
Researchers found that RbAp48 naturally helps other brain proteins called histones loosen their grip on a cell's DNA and directly affects the activation of genes that are responsible for brain function and memory.
To find RbAp48, researchers focused on the hippocampus, the region of the brain where memories are formed. After studying eight healthy brains donated to science by people between the ages of 33 and 88, they found that RbAp48 was reduced by nearly 50 percent in the older brains.
The researchers found that when they turned off RbAp48 in younger mice, they became more forgetful, while increasing RbAp48 in older mice restored memory. The mice were given memory tests that included object recognition and water maze problems.
Alzheimer’s vs. Age-Related Memory Loss
Age-related memory loss and Alzheimer’s are often mistakenly lumped together under the umbrella of “dementia.”
“Alzheimer's affects memory by acting on the hippocampal subregion known as the entorhinal cortex, while normal aging affects memory by targeting another region of the hippocampus, the dentate gyrus,” Pavlopoulos says. “To develop effective therapeutic approaches for these disorders, the correct targets must be found. We identified a specific target for age-related memory loss: RbAp48.”
And this insight may, in time, also help scientists as they search for Alzheimer's cures. “[Normal] cognitive aging happens to everyone, including people who develop Alzheimer’s,” Pavlopoulos says. “Might neurons that are resistant to aging be more resistant to the pathological insults that lead to Alzheimer’s disease?”
Is a Fix on the Way?
As with most studies, while exciting, these findings don't necessarily point to a cure for age-related memory loss; though they do highlight a potential drug pathway. It's important to note that the human tissue tested was from healthy—albeit deceased—human brains and that while mice can experience naturally occurring age-related memory loss, the same cannot be said for Alzheimer's disease, says Pavlopoulos.
"Our findings have the potential to be successfully applied to humans and to be translated into therapies for age-related memory decline. It is premature, however, to say that we have discovered a treatment for age-related memory loss, but the fact that we were able to reverse age-related memory loss in mice is very encouraging," he says.