Specific Genetic Factors Plus Unhealthy Diet Boost Risk of Alzheimer’s Disease, USC Study Finds

A high-fat, high-sugar diet may increase the risk of Alzheimer’s disease in people carrying the ApoE4 gene, according to a new study, “Obesity Accelerates Alzheimer-Related Pathology in APOE4 but Not APOE3 Mice,” that appeared in the journal eNeuro.

Obesity is considered an environmental risk factor for Alzheimer’s, while the strongest genetic risk factor for late onset of this disease is the ApoE4 gene.

ApoE proteins help regulate levels of cholesterol in the blood and transport fat molecules to the brain. However, high levels of the ApoE4 variant — one of possible version of the ApoE gene — have been associated with increased risk of heart disease, accelerated cognitive decline during aging and Alzheimer’s disease.

Science has shown that Alzheimer’s affects more women than men. Having one copy of ApoE4 quadruples women’s risk for developing the disease. But having two copies of ApoE4 is an issue for men and women, raising their risk for the disease by a factor of 10.

To understand the relationship between obesity and the ApoE genes, researchers at the University of Southern California compared the effects of a high-calorie diet in mice carrying either the relatively rare ApoE4 gene (present in 10-15 percent of the population) or the ApoE3 gene, a much more common variant not associated with Alzheimer’s disease (and found in 70-75 percent of the population).

For 12 weeks, mice with these genes were either fed a healthy diet composed of 10 percent fat and 7 percent sugar, or a Western diet, with 45 percent fat and 17 percent sugar.

Results showed that the unhealthy diet led to weight gain and pre-diabetes in mice with either gene. However, mice with the ApoE4 variant developed Alzheimer’s plaques in their brains, while no such damage was seen in mice with the ApoE3 gene. This suggests that people with different genetic backgrounds may be at different risk of developing Alzheimer’s. Consequently, those carrying the ApoE4 gene should pay more attention to what they eat.

“Part of what the results are saying is that risk doesn’t affect everybody the same, and that’s true for most risk factors,” Christian Pike, the study’s leading author, said in a news release. “Your genes have a big role in what happens to you, but so does your environment and your modifiable lifestyle factors. How much you exercise becomes important, and what you eat becomes important.”

More studies are warranted to further uncover the association between obesity, the ApoE4 gene and Alzheimer’s disease. Previous studies have suggested that unhealthy diets promote the activation of glia, brain cells responsible for inflammation.

“That means there are probably components directly in the diet, and one of those are fatty acids, like palmitic acid, that trigger inflammation because they can go in and directly affect glia,” Pike said. “But that may be just one inflammation-related component of Alzheimer’s disease.”

Research has also shown that women are more prone to develop Alzheimer’s disease than men. According to Pike, men and women with risk factors for Alzheimer’s disease may respond differently to diet, which is another important issue to study.