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Mouse
experiments suggest that folic acid could play an essential role in
protecting the brain against the ravages of Alzheimer's disease and
other neurodegenerative disorders, according to scientists at the
National Institute on Aging. This animal study* could
help researchers unravel the underlying biochemical mechanisms involved
in another recent finding that concluded people with high blood levels
of homocysteine have nearly twice the risk of developing the disease**.
In the
study, published in the March 1, 2002 issue of the Journal of Neuroscience,
the investigators fed one group of mice with Alzheimer's-like plaques
in their brains a diet that included normal amounts of folate, while
a second group was fed a diet deficient in this vitamin. . These mice
are transgenic, meaning they were bred with mutant genes that cause
AD in people. They develop AD-like plaques in their brains that kill
neurons.
The
NIA team counted neurons in the hippocampus, a brain region critical
for learning and memory that is destroyed as plaques accumulate during
Alzheimer's disease. The investigators found a decreased number of
neurons in the mice fed the folic acid deficient diet.
The
scientists also discovered that mice with low amounts of dietary folic
acid had elevated levels of homocysteine, an amino acid, in the blood
and brain. They suspect that increased levels of homocysteine in the
brain caused damage to the DNA of nerve cells in the hippocampus.
In transgenic mice fed an adequate amount of folate, nerve cells in
this brain region were able to repair damage to their DNA. But in
the transgenic mice fed a folate-deficient diet, nerve cells were
unable to repair this DNA damage.
"These
new findings establish a possible cause-effect relationship between
elevated homocysteine levels and degeneration of nerve cells involved
in learning and memory in a mouse model of Alzheimer's disease,"
said Mark Mattson, Ph.D., chief of the NIA's Laboratory of Neurosciences
and the study's principal investigator.
People
who have Alzheimer's disease often have low levels of folic acid in
their blood, but it is not clear whether this is a result of the disease
or if they are simply malnourished due to their illness. But based
on emerging research, Dr. Mattson speculates consuming adequate amounts
of folic acid -- either in the diet or by supplementation -- could
be beneficial to the aging brain and help protect it against Alzheimer's
and other neurodegenerative diseases.
Green
leafy vegetables, citrus fruits and juices, whole wheat bread and
dry beans are good sources of the vitamin. Since 1998, the Food and
Drug Administration has required the addition of folic acid to enriched
breads, cereals, flours, corn meals, pastas, rice, and other grain
products. However, because it can take a long time for the symptoms
of Alzheimer's disease to surface, researchers speculate it will be
many years before folate supplementation in food could affect the
incidence of dementia in the United States. A human clinical trial
is being planned.
In AD,
plaques develop first in areas of the brain used for memory and other
cognitive functions. They consist of largely insoluble deposits of
a protein called beta-amyloid. Although researchers still do not know
whether amyloid plaques themselves cause AD or whether they are by-products
of the AD process, there is evidence that amyloid deposition may be
a central process in the disease. But unlike human brain cells, the
brain cells in laboratory mice are not killed by the progressive accumulation
of beta amyloid. This finding led Dr. Mattson and his research team
to suspect folic acid or some other component of the mouse diet might
help these nerve cells resist beta amyloid damage. In earlier work,
Dr. Mattson found evidence suggesting folic acid deficiency can increase
the brain's susceptibility to Parkinson's disease.
The
NIA leads the Federal effort to support and conduct basic, clinical,
and social and behavioral studies on aging and AD. It supports the
Alzheimer's Disease Education and Referral (ADEAR) Center, which provides
information on AD research, including clinical trials, to the public,
health professionals, and the media. ADEAR can be contacted toll free
at 1-800-438-4380
weekdays or by visiting the website www.alzheimers.org.
Press releases, fact sheets, and other materials about aging and aging
research can be viewed at the NIA's general information website, www.nia.nih.gov.
*
I. Kruman, T.S. Kumaravel, A. Lohani, W. Pedersen, R.G. Cutler, Y.
Kruman, N. Haughey, J. Lee, M. Evans, and M.P. Mattson, "Folic
Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal
Neurons and Sensitize Them To Amyloid Toxicity in Experimental Models
of Alzheimer's Disease," Journal of Neuroscience, 22:5,
pp. 1752-1762.
**
S. Sesdradri, A. Beiser, J. Selhub, et al., "Plasma Homocysteine
As A Risk Factor For Dementia and Alzheimer's Disease," N
Eng J Med, 346:7, pp. 476-483.
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