WEDNESDAY, Aug. 28 (HealthDay News) -- A protein in the brain
could hold the key to reversing the age-related memory loss that
causes "senior moments" of forgetfulness, Columbia University
Deficiency of a protein called RbAp48 in the hippocampus appears
to significantly contribute to the memory loss that creeps up on
you as you age, said study co-author Dr. Scott Small, director of
the Alzheimer's Disease Research Center at the university.
This is a distinct process separate from the drastic memory loss
that comes with Alzheimer's disease, Small added. And, he said, the
finding should allay fears that normal "senior moments," like
misplacing keys or forgetting an ATM number, are a precursor to
"It's been known for a long time that our memory declines just by the normal wear and tear of the aging process," Small said. "Our study provides compelling evidence that age-related memory loss is a syndrome in its own right, apart from Alzheimer's."
The study, published Aug. 28 in the online edition of
Science Translational Medicine, used a combination of human
and mouse studies to explore the importance of RbAp48 in
Researchers focused on the hippocampus, a part of the brain that
is key to memory and is affected by both age-related memory loss
and by Alzheimer's disease. But while Alzheimer's is attributed to
the buildup of amyloid plaques in the brain's neurons, no such
thing occurs in people experiencing memory loss due to natural
The study began by researchers performing genetic analysis of
the brain cells of eight deceased humans, ages 33 to 88, none of
whom suffered from any brain disease. Doctors focused on the
dentate gyrus, a part of the hippocampus that seems to be most
affected by aging.
The most significant changes, they found, occurred in levels of
RbAp48 in the dentate gyrus. The amount of RbAp48 declined steadily
with aging across all the human subjects.
To confirm whether RbAp48 plays an active role in memory loss,
the researchers turned to mice. Examinations of mouse brains found
a similar decrease in the protein due to aging. "It turns out that
age-related memory loss occurs very similarly in humans and mice,"
Further, the researchers found that when they reduced the amount
of RbAp48 in young mice, those mice experienced the same memory
loss that occurs naturally in aging mice. Once the protein returned
to normal levels, the young mice's memory returned to normal.
But what really raised eyebrows occurred when they increased the
amount of RbAp48 in the brains of older 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 co-author Dr. Elias Pavlopoulos, an associate research
scientist at Columbia.
If these findings pan out, doctors may one day be able to use
this genetic pathway to improve aging people's memory through
natural or pharmaceutical means, Small said. Physical exercise,
dietary supplements or pharmaceuticals could be used to increase
RbAp48 in the hippocampus.
Dr. Nupur Ghoshal, an assistant professor of neurology at the
Washington University School of Medicine in St. Louis, agreed that
this study gives researchers a new take on exploring age-related
"Clinically, we've known that normal aging and Alzheimer's are different, but we didn't really have the thing to work on for normal aging," said Ghoshal, who was not involved with the study. "This is really the first evidence of a molecule someone can focus in on. Now we have a pathway we can learn a lot more about, and somewhere within that pathway may be a target for intervention."
Dean Hartley, the director of science initiatives at the
Alzheimer's Association, said the researchers "present an
intriguing, preliminary study that may eventually prove to be
important in uncovering the pathways of age-related memory
And, he added, "They provide some very elegant molecular
genetics to illustrate the mechanism in mice." However, the study's
results are weakened because only eight human brains were examined,
Hartley said, and the results in mice might not necessarily carry
over directly to humans.
"Nevertheless, there is enough preliminary data here that this line of investigation should go forward, especially in light of what it may contribute to our knowledge of 'normal' aging and the environmental factors affecting gene regulation," Hartley said.
For more about age-related memory loss, visit the
U.S. National Institute on Aging.
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