Omega-3 Fatty Acid May Help Prevent Alzheimer's Brain Lesions

This study with genetically modified mice is the first to show that DHA, an omega-3 fatty acid, can slow the accumulation of tau, a protein that leads to the development of neurofibrillary tangles. Such tangles are one of two signature brain lesions of Alzheimer's disease. DHA also was found to reduce levels of the protein beta amyloid, which can clump in the brain and form plaques, the other Alzheimer's lesion.

Previous studies have shown that DHA may have therapeutic value for Alzheimer's patients, but this research is among the first to show that it may delay the onset of the disease. DHA is found in fish, eggs, organ meats, micro-algae, fortified foods and food supplements.

"We are greatly excited by these results, which show us that simple changes in diet can positively alter the way the brain works and lead to protection from Alzheimer's disease pathology," said Frank LaFerla, professor of neurobiology and behavior and co-author of the study.

LaFerla and his research team studied the effects of DHA in mice bred to develop the plaques and tangles associated with Alzheimer's disease. Mice in the control group were given food that mimics a typical American diet, with the ratio of omega-6 fatty acids to omega-3 fatty acids being 10:1. Studies indicate that a proper ratio is important to maintain health, with the ideal being 3:1 to 5:1. Typical Western diets contain unhealthy ratios ranging from 10:1 to 30:1. Omega-6 fatty acids are found in corn, peanut and sunflower oils.

Mice in three test groups were given food with a 1:1 ratio of omega-6 fatty acids to omega-3 fatty acids. One of these groups received supplemental DHA only, and two groups received DHA plus additional omega-6 fatty acids. After three months, mice in all of the test groups had lower levels of beta amyloid and tau than mice in the control group, but at nine months, only mice on the DHA diet had lower levels of both proteins. These results suggest that DHA works better on its own than when paired with omega-6 fatty acids.

The scientists also determined the mechanism by which DHA leads to lower levels of beta amyloid. DHA, they found, leads to lower levels of presenilin, an enzyme responsible for cutting beta amyloid from its parent, the amyloid precursor protein. Without presenilin, beta amyloid cannot be generated. When clumped into plaques, beta amyloid disrupts communication between cells and leads to symptoms of Alzheimer's disease.

This latest study adds to growing evidence that diet and lifestyle changes may reduce the risk of developing Alzheimer's disease. LaFerla and his team have previously shown that short but repeated learning sessions can slow the physical progression of Alzheimer's in mice, suggesting that the elderly can delay onset of the disease by keeping their minds active. The team also found that stress hormones appear to rapidly exacerbate the formation of plaques and tangles, suggesting that managing stress could slow the progression of Alzheimer's.

"Combined with mental stimulation, exercise, other dietary intakes, and avoiding stress and smoking, we believe that people can significantly improve their odds against this disease," said Kim Green, scientist and lead author on the DHA, learning and stress studies.

Alzheimer's is a progressive neurodegenerative disorder that affects more than 4.5 million adults in the United States. With an aging population, that number could approach 20 million by 2050. Five percent of people older than 65 have Alzheimer's, and up to one-half of people are affected by age 80.

 This research appears in the April 18 issue of The Journal of Neuroscience.

UCI scientists Hilda Martinez-Coria and Hasan Khashwji, along with Martek Biosciences Corp. researchers Eileen Hall, Karin Yurko-Mauro and Lorie Ellis worked on this study.

Martek funded the study, and two clinical trials evaluating DHA are under way. The first trial, sponsored by Martek and the National Institute on Aging and conducted by the Alzheimer's Disease Cooperative Study, is examining the effects of DHA in slowing the progression of cognitive and functional decline in patients with mild to moderate Alzheimer's disease. The second trial, also sponsored by Martek, is evaluating the effects of DHA on age-related cognitive decline in healthy, older adults with mild memory complaints.