Omega-3 fatty acid protects against neurodegeneration

[David Baxter PhD]

Omega-3 Fatty Acid Protects Against Neurodegeneration
September 2, 2004

NEW YORK (Reuters Health) Sept 01 - In a transgenic mouse model of Alzheimer's disease (AD), dietary supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) prevents the synaptic damage and memory loss associated with the disease, according to a paper in the September 2nd issue of Neuron.

However, when these transgenic mice consume a diet depleted of DHA, oxidative stress resulting in synaptic damage is much greater than occurs in control mice on the same diet.

Dr. Greg M. Cole, at University of California, Los Angeles, and his team found that transgenic mice expressing the human mutant amyloid precursor protein (Tg+ animals), in which brain amyloid deposition is abundant, experienced very little synaptic marker loss. Further investigation revealed that the high DHA content in their food was neuroprotective.

When 17-month-old mice were fed a diet depleted in DHA, the investigators observed decreased levels of DHA in the frontal cortex of TG+ mice, but not in Tg- mice.

The increased oxidative stress from depleted DHA in the Tg+ mice "is accompanied by postsynaptic caspase-mediated actin cleavage and the loss of the actin-regulating dendritic spine protein drebin" and postsynaptic density protein-95 (PSD-95), the authors report. When they examined brain tissue from patients with AD and control subjects, there were similar losses of drebrin and PSD-95 in the AD brains only.

Testing with the Morris water maze showed profound performance deficits when Tg+ mice were placed on a low DHA diet. These performance deficits were prevented by dietary DHA supplementation. Tg+ mice fed DHA were able to learn how to find hidden platforms in water maze, as were control mice on either a DHA-depleted or DHA-repleted diet.

Their findings are evidence that the combination of genetic and environmental risk factors -- such as DHA deficiency -- for AD can act synergistically to reduce synaptic proteins required for cognition, Dr. Cole's group maintains.

They speculate that patients with a genetic risk of AD may be more vulnerable than others to a lack of essential fatty acids. Their data thus "support the idea that increased DHA intake should be considered as a potential neuroprotective strategy for AD," they write.

Neuron 2004;43:633-645.

 

[David Baxter PhD]

Why fish seems to prevent Alzheimer's damage

Why Fish Seems to Prevent Alzheimer's Damage
Wednesday, September 01, 2004
By Sid Kirchheimer, WebMD Medical News

Study Shows DHA in Omega-3 Fatty Acid Lowers Alzheimer's Disease Risk

Sept. 1, 2004 -- New evidence may further explain why people who regularly eat heart-healthy fish seem to have a lower risk of developing Alzheimer's disease.

A new study indicates that high amounts of one of the omega-3 fatty acids found in salmon, mackerel, and herring -- docosahexaenoic acid, or DHA -- may protect against the memory loss caused by Alzheimer's, even when there are already brain lesions indicating advanced disease. The study also indicates that DHA may protect against brain cell damage, similar to that seen in Alzheimer's.

This discovery comes after a team of American and French researchers infused mice with a human Alzheimer's-causing gene so they would develop brain lesions like that seen in advanced Alzheimer's. The point was to monitor the rodents' disease progression and better determine how various environmental factors might influence Alzheimer's progression.

What they found was that even though the mice developed brain lesions like that found in advanced Alzheimer's, they still showed little evidence of memory loss or other disease symptoms.

Secret in Mouse Chow ... and Fish
"We looked and looked at what could be providing this protection against the cognitive deficits we usually see in Alzheimer's patients with these brain lesions," says researcher Greg Cole, PhD, professor of neurology at UCLA's David Geffen School of Medicine. "And when we looked at their diet, we were surprised to learn why."

Their commercial feed was abundant in these omega-3 fatty acids, and specifically DHA. "It was so rich in DHA that it closely resembled the Japanese diet," he tells WebMD.

That fish- and seaweed-rich diet, already known to be heart-healthy, has long been suspected of playing some role in the prevention of Alzheimer's. Several studies in recent years show that people who regularly eat diets high in DHA have a lower risk of developing Alzheimer's disease.

While the abundance of healthy polyunsaturated fats like DHA in certain fish has been considered a protection against Alzheimer's, one popular theory is that these heart-healthy fish might improve impeded blood flow to the brain. Other research shows that cholesterol-lowering statins and "blood-thinning" aspirin and other nonsteroidal anti-inflammatory drugs (NSAID) pain relievers may also lower risk of Alzheimer's by reducing inflammation or increasing blood flow.

"But our study suggests there's a causal relationship that's independent of vascular dementia or atherosclerosis," Cole tells WebMD. That's because his test mice carried the Alzheimer's gene, but did not have any indications of cardiovascular disease and blood flow abnormalities.

Specifically, his team reports in the latest issue of Neuron that DHA may prevent or slow Alzheimer's progression by protecting against damage to the area where brain cells communicate. Damage to these "synaptic" areas is known to impair memory and learning ability and typically occurs in Alzheimer's patients.

Eat Fish at Least Once a Week
After noting the mice chow was high in DHA, Cole's team switched the rodents to a diet rich in safflower oil, known to deplete the body's DHA stores, he says. One group, already with advanced brain lesions, got no additional DHA supplementation while the other, also with advanced lesions, was fed DHA-rich algae to regain beneficial levels.

After five months, the mice whose new diet was depleted of DHA showed high levels of synaptic damage that's consistent with advanced Alzheimer's deterioration. But the group getting high levels of DHA continued to perform well in memory tests, even though they carried the Alzheimer's gene. The conclusion: "The DHA-enriched diet was holding their genetic disease at bay," says Cole.

Martha Clare Morris, ScD, of the Rush Institute for Healthy Aging in Chicago, says these findings don't surprise her. She was not involved in Cole's research but last summer, she published a study in Archives of Neurology showing that people older than age 65 who ate omega-3-rich fish at least once a week were 60% less likely to develop Alzheimer's compared with those who rarely ate these fish.

"We looked at the different types of omega-3 fatty acids in relation to the risk of developing Alzheimer's, and of these acids, it was DHA that seemed to have a very strong protective association," she tells WebMD. "Still, it's a very interesting study."

Although DHA is also found in fish oil supplements, how these over-the-counter pills specifically impact the development or progression of Alzheimer's has not been carefully studied, she adds. Eggs laid by chickens fed a DHA-supplemented diet contain some DHA, as do almonds and walnuts, but the highest amounts come from cold-water fish.

"The few studies that show a benefit find that just one or two fish meals a week is where you see the benefit," says Morris.

Source: Calon, F. Neuron, Sept. 2, 2004; vol 43: pp 633-645. Morris, M. Archives of Neurology, July 2003; vol 60: pp 940-946. Greg Cole, PhD, professor of neurology, David Geffen School of Medicine at UCLA, Los Angeles. Martha Clare Morris, ScD, associate professor of epidemiology, Rush Institute for Healthy Aging, Chicago.