Researchers Discover Potential Clue behind Age-Related Memory Decline
Scientists from Columbia University improve memory in elderly mice after pinpointing a gene for senescent forgetfulness
When a loved one starts to forget names, faces, appointments or other details, waiting for the correct diagnosis can be agonizing.Image: ThinkStock
Forgetfulness is accepted as a natural part of getting older, but it might not have to be. Scientists say they have identified an important biological mechanism in the brain that underlies the sorts of memory lapses that come with age. The condition is familiar to just about anyone who has lived more than a few decades and is often marked by frustrated utterances like “Where did I park the car?” and “What am I doing here?”
The latest research, which was reported in the journal Science Translational Medicine,provides further support of the idea that this kind of forgetfulness is distinct from Alzheimer’s disease, and offers clues to how we might someday prevent or even reverse age-related memory decline.
The early stages of Alzheimer’s disease can be difficult to distinguish from the typical memory loss that accompanies aging. When a loved one starts to forget names, faces, appointments or other details, waiting for the correct diagnosis can be agonizing. The current study, led by Eric Kandel, a neuropsychiatrist at Columbia University who won the Nobel Prize in Physiology or Medicine in 2000 for his work on memory, might one day lead to a diagnostic test for common forgetfulness. The results could help to rule out Alzheimer’s disease earlier—before more unmistakable symptoms begin to appear—and “save people anxiety when they begin to have memory deficits,” Kandel says.
From a neurological point of view, Alzheimer’s disease and age-related memory decline both begin in the hippocampus, a structure in the brain that is involved in converting memory from short-term to long-term. But the problems caused by Alzheimer’s start in a section of the hippocampus called the entorhinal cortex and then spread to other parts of the brain whereas the trouble with age-related memory decline seems to affect primarily a part of the hippocampus called the dentate gyrus. Autopsy studies to date suggest that the latter is mostly untouched in Alzheimer’s patients.
In the first phase of their study Kandel and his team examined the brains of eight recently deceased people aged 33 to 88 who did not have any neurological disorders. The investigators looked for changes in gene activity that corresponded with signs of aging in the dentate gyrus but not in the surrounding tissue. After singling out 17 potentially responsible genes they found one—the gene for a protein called RbAp48—that seemed more promising than the others because levels of the protein were so much lower in the dentate gyri of the brains donated by elderly individuals.
The results of the brain tissue examination established a correlation between low RbAp48 levels and memory decline, but the researchers still could not tell if the drop was the reason behind the memory deficit in the first place, or if the presence of both was simply a matter of coincidence. To answer that question, the researchers tested the memory of mice that had been genetically engineered to be deficient in RbAp48./.../
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