Good Diets Fight Bad Alzheimer Genes

Diets high in fish oil have a beneficial effect in patients at risk

Scientists today agree that there are five molecules that are known to affect or cause Alzheimer’s disease, which plagues an estimated five million Americans. The potency of these molecules is linked to environmental factors such as diet and lifestyle.

Professor Daniel Michaelson of Tel Aviv University’s Department of Neurobiologyat the George S. Wise Faculty of Life Sciences has illuminating news about one of these five molecules — APOE, created by the apolipoprotein E gene found in all of our bodies.

Professor Michaelson says APOE comes in two forms, a “good” APOE gene and a “bad” APOE gene, called APOE4. He has developed animal models to investigate the effects of diet and environment on carriers of APOE4, the presence of which is a known risk factor for Alzheimer’s. It appears in 50% of all Alzheimer’s patients, and in 15% of the general population which due to APOE4 is the population which is at risk of getting the disease.

The good news? A diet high in Omega 3 oils and low in cholesterol appears to significantly reduce the negative effects of the APOE4 gene in mouse models.

Exercise is not enough — and may be worse

Prof. Daniel Michaelson

In differentiating between the good and bad variants of the APOE gene, Professor Michaelson and his team studied many variables. They determined that while a rich and stimulating environment is good for carriers of “good” APOE, the same environment has a negative effect on those at risk for Alzheimer’s because they carry the APOE4 gene. While this environment stimulated the formation of new neuronal connections in the “good APOE” mice, it caused the death of brain neurons in the “bad APOE” mice. The stimulating environment included running wheels and tubes for hiding and sliding, as well as ropes and other toys for the mice to play on, replaced and updated with new toys weekly. Those in a non-stimulating environment had access to no toys at all.

“Conditions that are generally considered good can be harmful if the mouse is a carrier of the APOE4 gene. Extrapolating this to the human population, individuals with the bad APOE4 gene are more susceptible to stress caused by an environment that stimulates their brain,” says Professor Michaelson.

The following is an abstract of a study by the research group of Professor Michaelson. The study is published in Journal of Alzheimer’s Disease (2012; 28 (3): 667-83):

“Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer’s disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (ω3)), a major brain polyunsaturated fatty acid, is protective for AD and that elevated cholesterol levels are an AD risk factor. We presently investigated the extent to which the pathological effects of apoE4 in vivo can be prevented by consuming fish oil (DHA) or can be modified by cholesterol. Accordingly, apoE3- and apoE4-targeted replacement mice were subjected, following weaning, to a fish oil dietenriched in DHA and to a cholesterol-containing diet under regular and enriched environments. Cholesterol metabolism in the hippocampus and the corresponding phospholipid and fatty acid levels were affected by fish oil (DHA) and cholesterol diets and by environmental stimulation. Importantly, cholesterol metabolism and the fatty acid levels were not affected by apoE4. The phospholipid levels were, however, affected by apoE4. This effect was most pronounced in the cholesterol-fed mice and was abolished by the fish oil (DHA) diet. ApoE4 elevated hippocampal intraneuronal amyloid-β levels under regular conditions and lowered them following environmental stimulation, relative to those of the apoE3 mice. ApoE4 also elevated the levels of the presynaptic transporters Vglut and Vgat, and decreased behavioral performance in an object recognition test. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA)diet could be used to attenuate the effects of apoE4 in AD.”

When it’s good, it’s good

“The main take-away message here is that good diets can alleviate the effects of bad genes. Of course nutritionists have had this general idea for a while, but it’s nice to be able to show that this approach can be applied to specifically counteract the negative effects of Alzheimer’s disease-related genes,” says Professor Michaelson.

 

 Reference

Kariv-Inbal Z, Yacobson S, Berkecz R, Peter M, Janaky T, Lütjohann D, Broersen LM, Hartmann T, Michaelson DM. The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. J Alzheimers Dis 2012; 28 (3): 667-83.

 

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