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Health News Archive 44 - Brain and Alzheimer's (con't)
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UCLA-VA Study Names Curcumin as Potential Alzheimer's Weapon

A new UCLA-Veterans Affairs study involving genetically altered mice suggests that curcumin, the yellow pigment in turmeric, a curry spice, inhibits the accumulation of destructive beta amyloids in the brains of Alzheimer's patients and also breaks up existing plaques.

Reporting in the Dec. 7, 2004, online edition of the Journal of Biological Chemistry, the research team also determined curcumin is more effective in inhibiting formation of the protein fragments than many other drugs being tested as Alzheimer's treatments. The researchers found the low molecular weight and polar structure of curcumin allow it to penetrate the blood-brain barrier effectively and bind to beta amyloid.

In earlier studies (Journal of Neuroscience, 2001; 21:8370-8377; Neurobiology of Aging, 2001; 22:993-1005), the same research team found curcumin has powerful antioxidant and anti-inflammatory properties, which scientists believe help ease Alzheimer's symptoms caused by oxidation and inflammation.

The research team's body of research into curcumin has prompted the UCLA Alzheimer's Disease Research Center (ADRC) to begin human clinical trials to further evaluate its protective and therapeutic effects. More information about enrolling in this and other clinical trials at the Center is available by calling (310) 206-3779 or online at .

"The prospect of finding a safe and effective new approach to both prevention and treatment of Alzheimer's disease is tremendously exciting," said principal investigator Dr. Gregory Cole. He is professor of medicine and neurology at the David Geffen School of Medicine at UCLA, associate director of the UCLA Alzheimer's Disease Research Center, and associate director of the Geriatric Research, Education and Clinical Center at the VA Greater Los Angeles Healthcare System at Sepulveda, Calif.

"Curcumin has been used for thousands of years as a safe anti-inflammatory in a variety of ailments as part of Indian traditional medicine," Dr. Cole said. "Recent successful studies in animal models support a growing interest in its possible use for diseases of aging involving oxidative damage and inflammation like Alzheimer's, cancer and heart disease. What we really need, however, are clinical trials to establish safe and effective doses in aging patients."

The research was funded by the Siegel Life Foundation, Veterans Affairs, Alzheimer's Association, UCLA Alzheimer's Disease Research Center and private donors.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that occurs gradually and results in memory loss, unusual behavior, personality changes, and a decline in thinking abilities. These losses relate to the death of brain cells and the breakdown of the connections between them. The disease is the most common form of dementing illness among middle and older adults, affecting more than 4 million Americans and many millions worldwide. The prevalence of Alzheimer's among adults ages 70-79 in India, however, is 4.4 times less than the rate in the United States.

Widely used as a food dye and preservative, and in some cancer treatments, curcumin has undergone extensive toxicological testing in animals. It also is used extensively in traditional Indian medicine to treat a variety of ailments.

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Quercetin Minimizes Brain Cell Damage from Alzheimer's

Rat brain cells exposed to the antioxidant quercetin resisted cell damage much better than those not treated, a research team at Cornell University in New York reported.

Antioxidants are compounds that counteract the damage done by chemicals known as free radicals -- generated by sunlight, chemical reactions and the stress of day-to-day living. The researchers say their study adds strength to the theory that the risk of developing Alzheimer's and similar brain diseases might be reduced by eating plenty of fresh fruits and vegetables or taking supplements.

Writing in the December 1, 2004 issue of the Journal of Agricultural and Food Chemistry, the Cornell team said they soaked rat brain cells in either quercetin or vitamin C -- another potent antioxidant. The cells were then exposed to hydrogen peroxide to mimic the type of oxidative cell damage that is believed to occur with Alzheimer's disease.

Brain cells that were treated with quercetin had significantly less damage than the cells treated with vitamin C and cells that were not treated with antioxidants.

"On the basis of serving size, fresh apples have some of the highest levels of quercetin when compared to other fruits and vegetables and may be among the best food choices for fighting Alzheimer's," C.Y. Lee, a professor and chairman of the Department of Food Science & Technology at Cornell University, who led the study, said in a statement.

Lee said the skins of apples contain the highest levels of quercetin so juice is not necessarily the best source. In general, red apples tend to have more of the antioxidant than green or yellow ones, he said. Other foods high in quercetin include onions, blueberries and cranberries.

SOURCE: Ho Jin Heo and Chang Yong Lee. Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration. J. Agric. Food Chem., 52 (25), 7514 -7517, 2004.

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Omega-3 Fatty Acids Protect Against Alzheimer's Disease

Omega-3 fatty acids, found in soy, fish and other oils, and known to provide a range of health benefits, may help protect against Alzheimer's disease, U.S. researchers reported.

Tests on mice showed that a diet high in one particular omega-3 fatty acid called DHA helped protect the brain against the memory loss and cell damage caused by Alzheimer's disease. "We saw that a diet rich in DHA, or docosahexaenoic acid, dramatically reduces the impact of an Alzheimer's gene, said Dr. Greg Cole, a Professor of Neurology at the University of California Los Angeles School of Medicine.

In the journal Neuron, Dr. Cole and colleagues reported the results of studies with mice bred to have genetic mutations that cause brain lesions associated with Alzheimer's disease. The investigators were looking for something else, but noticed the mice did not have the expected memory loss or brain damage. Notably, the synapses, the connections between brain cells, were not as damaged as would be expected. "We discovered that the mice lived on a nutritious diet of soy and fish -- two ingredients chock-full of omega-3 fatty acids," said Sally Frautschy, who worked on the study.

"Because earlier studies suggest that omega-3 fatty acids may prevent Alzheimer's disease, we realized that the mice's diet could be countering the very thing we were trying to accomplish -- showing the progression of the Alzheimer's-related brain damage," she added in a statement. The researchers removed fish and soy from the mouse diet and substituted safflower oil instead, which is low in omega-3 and rich in another fatty acid called omega-6, which does not include DHA. Some mice stayed on the original diet and others got the new, less-healthy diet.

"We found high amounts of synaptic damage in the brains of the Alzheimer's-diseased mice that ate the DHA-depleted diet," Frautschy said. "These changes closely resembled those we see in the brains of people with Alzheimer's disease." Mutant mice on the DHA-rich diet did better on memory tests than the mice fed safflower oil, the researchers said.

"After adjusting for all possible variables, DHA was the only factor remaining that protected the mice against the synaptic damage and memory loss that should have resulted from their Alzheimer's genes," said Cole. "We concluded that the DHA-enriched diet was holding their genetic disease at bay."

People are already advised to eat omega-3 fatty acids to protect the heart.

DHA and a related fatty acid called AHA are also added to some infant formulas and milks to promote brain development. They are found naturally in human breast milk.

SOURCE: Neuron, September 2, 2004.

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Drinking Tea Might Delay Alzheimer's Disease

Drinking tea appears to affect the brain in a similar way as drugs prescribed for Alzheimer's disease, UK researchers report. The team, based at Newcastle University's Medicinal Plant Research Centre, investigated the properties of green and black tea, as well as coffee, in a series of laboratory experiments. Their study was published in the August 2004 edition of Phytotherapy Research.

The results showed that both green and black tea inhibited the activity of enzymes associated with the development of Alzheimer's disease. Coffee, however, had no significant effect.

The teas inhibited the activity of acetylcholinesterase -- the same mechanism of action used by drugs such as Novartis' Exelon and Pfizer's Aricept. The teas also hindered the activity of the butyrylcholinesterase, which has been found in senile plaques in the brains of Alzheimer's disease patients. Green tea obstructed the activity of beta-secretase, which also plays a role in the production of senile plaques, and is the focus of research by companies such as Ireland's Elan.

"Although there is no cure for Alzheimer's, tea could potentially be another weapon in the armoury which is used to treat this disease and slow down its development," lead researcher, Dr. Ed Okello, said. However, he added that there is no published evidence showing that rates of Alzheimer's disease are any lower in tea-loving countries such as Britain, China and Japan.

The researchers are seeking funds to find out which components of green tea inhibit the activity of the three enzymes and hope ultimately to develop a medicinal tea for Alzheimer's disease patients.

SOURCE: Phytotherapy Research, August 2004.

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Curcumin Protects the Brain Against Free Radical Damage

Curcumin, a component of turmeric and curry, enhances an enzyme that protects the brain against free radical damage, according to a paper presented at the Experimental Biology conference in April, 2004. The study paves the way for further research to determine if curcumin could prevent or reduce the progression of age-related neurodegenerative disorders such as Alzheimer's disease.

The human body possesses certain genes that regulate antioxidant activity. One of these genes, hemeoxygenase-1 (HO-1), is thought to defend brain cells that are exposed to oxidant challenges. In past studies, curcumin strongly encouraged the expression and activity of HO-1 in rat cells, indicating that curcumin can help blunt the effects of oxidation.

In order to confirm these previous findings, and determine if curcumin could have the same effects in brain cells, researchers in the current study investigated curcumin's neuroprotective effects and its ability to induce HO-1 in cultured hippocampal neurons. Treatment with curcumin resulted in increased expression of HO-1 as well as a greater expression of antioxidant enzymes. Pre-incubation of the cells with curcumin resulted in enhanced cellular resistance to oxidative damage.

According to the researchers, the study indicates that curcumin could be used for therapeutic purposes as a powerful inducer of HO-1 that can protect brain cells against oxidative damage. The study authors call for additional in vitro and in vivo studies to determine if curcumin can prevent acute neurodegenerative conditions.

Reference:  Scapagnini G, Colombrita C, Calabrese C, Pascale A, Schwartzman ML, Abraham NG. 'Curcumin Cytoprotective Effect in Rat Astrocytes and Neurons is Mediated by Specific Induction of HO-1', presented at Experimental Biology 2003 Conference, Washington, D.C., April 17 - 21, 2004.

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DHEA Increases Growth of Human Brain Cells

The hormone dehydroepiandrosterone (DHEA) significantly increases the growth rate of human brain cells, new research indicates.

Researchers tested DHEA on human neural stem cells. They also tested pregnenolone, which the human body converts into DHEA, as well as six of DHEA's metabolites.

Although pregnenolone and DHEA's metabolites had no effect on the stem cells, DHEA treatment caused up to a 29 percent increase in the number of neurons produced by the stem cells. This finding suggests that DHEA may help the body produce new brain cells with age. The finding also supports past research that indicates DHEA may enhance memory and indicates a potential role for DHEA in dementias such as Alzheimer's disease.

According to the researchers, 'Together this data suggests that DHEA is involved in the maintenance and division of human neural stem cells. Given the wide availability of this neurosteroid, this finding has important implications for future use.'

Suzuki M, Wright LS, Marwah P, Lardy HA, Svendsen CN. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3202-7. Epub 2004 Feb 18.

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Increased Fish and Omega-3 Fish Oil Intake Associated With Reduced Risk of Alzheimer's

Results from a study released in November, 2003 conducted at Tufts University suggest that having increased docosahexaenoic acid (DHA) levels in the blood and eating about three fish meals each week are associated with a significant 48 percent reduction in the risk of Alzheimer's disease in elderly men and women.

Researchers at Tufts University in Boston measured the fatty acid content of plasma obtained from 1137 men and women with a mean age of 75 who were part of the Framingham Heart Study. The subjects' diets were assessed by questionnaire and those free of dementia were followed for an average of 10 years. During the study they were assessed for the onset of new dementia including Alzheimer's Disease.

Participants who had diets rich in DHA, an omega-3 fatty acid, reduced their risk of developing dementia considerably compared with those whose diets contained low amounts of DHA.  DHA, or docosahexaenoic acid, is the most abundant fatty acid in the brain. Besides a diet that includes fish, another way to obtain DHA is by supplementation. These results are consistent with a study published in Archives of Neurology in July, 2003.

"These dramatic results show how older adults can play a significant role in their neurological health by increasing their intake of fish, fish oil or especially, DHA," said Ernst Schaefer, M.D., senior scientist and director of the Lipid Metabolism Laboratory at Tufts University.

"Until now there have only been two predictors for Alzheimer's Disease, age and genotype," stated Henry Linsert, Jr., Chairman and CEO of Martek. "This study suggests that low dietary intake of DHA may be a risk factor for Alzheimer's Disease.

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