Scientists have found a compelling clue in the quest to learn what causes
age-related memory problems and to one day be able to tell if those misplaced
car keys are just a "senior moment" or an early warning of something worse.
Wednesday's report offers evidence that age-related memory loss really is a
distinct condition from pre-Alzheimer's -- and offers a hint that what we now
consider the normal forgetfulness of old age might eventually be treatable.
Researchers at Columbia University Medical Center examined brains, young and
old, donated from people who died without signs of neurologic disease. They
discovered that a certain gene in a specific part of the hippocampus, the
brain's memory center, quits working properly in older people. It produces less
of a key protein.
That section of the brain, called the dentate gyrus, has long been suspected of
being especially vulnerable to aging. Importantly, it's a different neural
neighborhood than where Alzheimer's begins to form.
But it's circumstantial evidence that having less of that protein, named RbAp48,
affects memory loss in older adults. So the researchers took a closer look at
mice, which become forgetful as they age in much the same way that people do.
Sure enough, cutting levels of the protein made healthy young rodents lose their
way in mazes and perform worse on other memory tasks just like old mice
More intriguing, the memory loss was reversible: Boosting the protein made
forgetful old mice as sharp as the youngsters again, the researchers reported in
the journal Science Translational Medicine.
"It's the best evidence so far" that age-related memory loss isn't the same as
early Alzheimer's, says Nobel laureate Eric Kandel, who led the Columbia
And because some people make it to 100 without showing much of a cognitive
slowdown, the work brings another question: "Is that normal aging, or is it a
deterioration that we're allowing to occur?" Kandel said.
Adds Columbia neurologist Scott Small, a senior author of the study: "As we want
to live longer and stay engaged in a cognitively complex world, I think even
mild age-related memory decline is meaningful. It opens up a whole avenue of
investigation to now try to identify interventions."
The research is in the early stage and will require years of additional work to
confirm, cautions Molly Wagster of the National Institute on Aging, who wasn't
involved with the report. But she says the findings add to a growing body of
evidence suggesting "that we're not all on the road to Alzheimer's disease"
after we pass a certain age.
For example, other researchers have found that connections between neurons in
other parts of the brain weaken with normal aging, which makes it harder but not
impossible to retrieve memories. In contrast, Alzheimer's kills neurons.
How does Wednesday's research fit? Many pathways make up a smoothly functioning
memory, and that protein plays a role in turning a short-term memory -- like
where you left those car keys -- into a longer-term one, Kandel explains.
Some good news: Scientists already know that exercise makes the dentate gyrus --
that age-targeted spot in the hippocampus -- function better, Small says. He's
also studying whether nutrition might make a difference.