Alzheimer’s currently afflicts an estimated 5.1 million Americans. By 2050, the number of individuals age 65 and over with Alzheimer’s could range from 11 million to 16 million unless science finds a way to prevent or effectively treat the disease.
Studies have revealed the effects substances in the environment or our diet on either the promotion or slowing of symptoms associated with Alzheimer’s.
Fish oil elevated the level of a protein that prevents the formation of amyloid, which makes up amyloid plaques found in Alzheimer’s.
Caffeine reversed memory impairment in animal models of the disease.
Environmental copper reduced the clearance of amyloid from the brain to blood.
Researchers have identified ways that essential omega-3 fatty acid, docosahexaenoic acid (DHA) or fish oil, can help prevent Alzheimer’s. This substance is found in fatty fish like salmon.
The findings are based on the realization that a common form of Alzheimer’s in the elderly appears to be caused by a mix of genetic and environmental risks that speed the buildup of the sticky protein amyloid that forms brain lesions. A recently identified genetic risk factor for Alzheimer’s reduces levels of a protein called LR11 that prevents amyloid formation, most old people with Alzheimer’s tend to have low levels of LR11.
In recent studies, increased DHA consumption resulted in an increase of the LR11 protein, says Gregory Cole, PhD, of the Greater Los Angeles Veterans Administration Medical Center and the University of California, Los Angeles. “Inheriting low levels of LR11 appears to increase our risk for Alzheimer’s by increasing production of the toxic peptide believed to cause the disease. Raising LR11 levels through diet should have the opposite effect and be protective,” Cole says. “We find that low doses of DHA increase the levels of LR11 in rat primary neurons and human neuronal cells in culture, while dietary DHA increases LR11 in brains of aged control and DHA-depleted Alzheimer’s mice and other animal models.”
A University of California, Irvine, group found that DHA also reduced levels of tau protein in an animal model. Tau is another substance that builds up in Alzheimer’s and damages brain cells essential for learning and memory. Tau buildup is caused by increased activity of enzymes that act on tau called tau kinases, which causes the tau protein to misfold and clump, forming neurofibrillary tangles. Feeding mouse models of Alzheimer’s on a DHA-depleting diet increased the activity of an important tau kinase enzyme; conversely, adding DHA back to the diet reduced active tau kinases. The same tau kinase enzymes not only cause tau buildup, they also inactivate and cause loss of a protein that is essential for normal insulin and other neuroprotective activity.
DHA also reduced pro-inflammatory arachidonic acid in brains of Alzheimer’s model mice, consistent with the anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) that are associated with reduced Alzheimer’s in people. NSAIDs inhibit enzymes that make some important arachidonic acid products. “Collectively, our results and observations from other groups argue that DHA can intervene at five or more steps that occur early in the path to Alzheimer’s,” Cole says.
“Because DHA and DHA-rich fish oil have all of these activities and are still cheap and very safe, they should be seriously considered for dementia prevention trials,” says Cole.
In other research, caffeine, the most widely taken psychoactive drug in the world, could provide a surprisingly effective treatment against Alzheimer’s, if taken in the right amounts, says Gary Arendash, PhD, of the Byrd Alzheimer’s Institute in Tampa, Fla. He and his colleagues show that long-term caffeine intake may have the potential to delay or reduce the risk of Alzheimer’s.
“Our study shows that the memory impairment of aged Alzheimer’s mice was completely reversed by giving them caffeine, the human equivalent of five daily cups of coffee, in their drinking water,” Arendash says. In addition, evidence of Alzheimer’s in the brains of mice given caffeine was found to be substantially decreased, indicating that caffeine has a direct effect on the Alzheimer’s disease process and is not simply masking symptoms. On the basis of these studies in Alzheimer’s mice, the Byrd Alzheimer’s Institute has begun Phase II clinical trials with caffeine in aged humans.
“Not only does caffeine appear to offer promise as an effective treatment against Alzheimer’s, but our prior work has determined that the same daily amount of caffeine protects Alzheimer’s mice from even getting memory impairment to begin with, when caffeine treatment is started in young adulthood,” Arendash says. Caffeine may have the potential of both preventing and treating Alzheimer’s disease when taken in moderate amounts, about 500 mg daily-five cups of coffee, with each cup containing 100 mg, he says.
In other research, scientists also are finding evidence for a new role for copper in promoting the amyloid hypothesis of Alzheimer’s disease. Copper is an essential element for many bodily functions, including those involving metabolism, the brain, blood vessels, and bone. However, excess free unbound copper, copper that is not held within specific proteins in the body, is toxic. Copper is increased in blood vessels of the aging brain and also is found to be attached to Alzheimer’s toxins in the brain.
Copper was found to reduce the clearance of amyloid from the brain to blood and enhance the degradation of the main carrier of amyloid-ß across brain blood vessels, says Rashid Deane, PhD, of the University of Rochester.
In Deane’s research, mice were treated with low levels of copper, about one-tenth of the U.S. Environmental Protection Agency’s acceptable levels for drinking water, and cells from human brain blood vessels, obtained from autopsies, were mixed with low levels of copper. They showed that in comparison to controls, mice treated with trace copper levels in their drinking water had increased copper levels in blood vessels in the brain, decreased levels of the main carrier of amyloid in these vessels, and increased amyloid toxin accumulation in the brain. In the normal brain, there is evidence that amyloid is cleared by rapid transport from brain to blood mainly by the carrier protein. In the Alzheimer’s brain, the levels of the carrier protein in the blood vessels are reduced, and consequently the toxins are increased in brain.
Copper adheres strongly to amyloid and may promote its accumulation and toxicity. The accumulation of copper in brain blood vessels over a long period may reduce carrier protein levels and contribute to toxic amyloid accumulation in the brain, which consequently kills brain cells, as seen in Alzheimer’s.
“Our findings offer a possible mechanism for the reduction of carrier protein levels in brain blood vessels in the aging brain and suggest that this may contribute to Alzheimer’s. This is the first time this novel information is presented,” Deane says. “The next step is to further characterize the mechanism of this new role of copper and clarify its role in humans. It will also be important to determine if ingesting environmental copper may contribute to the development of Alzheimer’s.”
1. Society for Neuroscience.
2. National Institute on Aging.