|Exercise Slows Development of Alzheimer’s-Like
Brain Changes in Mice, New Study Finds
Physical activity appears to inhibit Alzheimer's-like
brain changes in mice, slowing the development of a
key feature of the disease, according to a new study.
The research demonstrated that long-term physical activity
enhanced the learning ability of mice and decreased
the level of plaque-forming beta-amyloid protein fragments — a
hallmark characteristic of Alzheimer's disease (AD) — in
A number of population-based studies suggest that
lifestyle interventions may help to slow the onset and
progression of AD. Because of these studies, scientists
are seeking to find out if and how physically or cognitively
stimulating activity might delay the onset and progression
of Alzheimer's disease. In this study, scientists have
now shown in an animal model system that one simple
behavioral intervention — exercise — could
delay, or even prevent, development of AD-like pathology
by decreasing beta-amyloid levels.
Results of this study, conducted by Paul A. Adlard,
Ph.D., Carl W. Cotman, Ph.D., and colleagues at the
University of California, Irvine, are published in the
April 27, 2005, issue of The Journal of Neuroscience.
The research was funded in part by the National Institute
on Aging (NIA), a component of the National Institutes
of Health, U.S. Department of Health and Human Services.
Additional funding was provided by the Christopher Reeve
To directly test the possibility that exercise (in
the form of voluntary running) may reduce the cognitive
decline and brain pathology that characterizes AD, the
study utilized a transgenic mouse model of AD rather
than normal mice. The transgenic mice begin to develop
AD-like amyloid plaques at around 3 months of age. Initially,
young mice (6 weeks or 1 month of age) were placed in
cages with or without running wheels for periods of
either 1 month or 5 months, respectively. Mice with
access to running wheels had the opportunity to exercise
any time, while those without the wheels were classified
On 6 consecutive days after the exercise phase, the
researchers placed each mouse in a Morris water maze
to examine how fast it could learn the location of a
hidden platform and how long it retained this information.
(This water maze task involves a small pool of water
with a submerged platform that the mouse must learn
how to find.) The animals that exercised learned the
task faster. Thus the mice that used the running wheels
for 5 months took less time than the sedentary animals
to find the escape platform. The exercised mice acquired
maximal performance after only 2 days on the task, while
it took more than 4 days for the sedentary mice to reach
that same level of performance. This suggests that exercise
may help to offset learning/cognitive deficits present
in AD patients.
Next, the investigators examined tissues from the
brains of mice that had exercised for 5 months. They
compared the levels of plaques, beta-amyloid fragments,
and amyloid precursor protein, a protein found throughout
the body and from which the beta-amyloid peptide is
derived. In AD, beta-amyloid fragments clump together
to form plaques in the hippocampus and cerebral cortex,
the brain regions used in memory, thinking, and decision
Compared to the sedentary animals, mice that had exercised
for 5 months on the running wheels had significantly
fewer plaques and fewer beta-amyloid fragments (peptides)
in the cerebral cortex and hippocampus, approximately
by 50 percent. Additional studies, of exercised animals
at 10 weeks old, showed that the mechanism underlying
this difference began within the first month of exercise.
"These results suggest that exercise — a simple
behavioral strategy — in these mice may bring
about a change in the way that amyloid precursor protein
is metabolized," says D. Stephen Snyder, Ph.D., director
of the etiology of Alzheimer's program in the NIA's
Neuroscience and Neuropsychology of Aging Program. "From
other research, it is known that in the aging human
brain, deposits of beta-amyloid normally increase. This
study tells us that development of those deposits can
be reduced and possibly eliminated through exercise,
at least in this mouse model."
These findings follow another recent report of a link
between an enriched environment and Alzheimer's-like
brain changes. That study, published Orly Lazarov, Ph.D.,
and colleagues in the March 11, 2005, issue of the journal Cell,
found that beta-amyloid levels decreased in the brains
of another kind of transgenic mice when they were housed
in groups and in environments that were enriched with
running wheels, colored tunnels, and toys.
"Both of these studies are exciting because they offer
insight into one of the pathways through which exercise
and environment might promote resistance to development
of cognitive changes that come with aging and AD," Snyder
notes. "It is as though exercise or environmental enrichment
forces the metabolism of amyloid precursor protein through
a pathway that is less harmful and might even be beneficial.
Further research will help us to understand those mechanisms,
to learn how much and what kind of exercise is best,
and to see if these same effects occur in humans."
For more information on participation in an AD clinical
trial, visit http://www.clinicaltrials.gov/ (search
for Alzheimer's disease trials), or the Alzheimer's
Disease Education and Referral (ADEAR) Center website
ADEAR may also be contacted toll free at 1-800-438-4380.
The ADEAR Center is sponsored by the NIA to provide
information to the public and health professionals about
AD and age-related cognitive change and may be contacted
at the website and phone number above for a variety
of publications and fact sheets, as well as information
on clinical trials.