In a mouse study, researchers dove into the complicated tangle of genetics and diet to figure out what really drives Alzheimer's risk.
We all know that a diet lacking in nutrition leads to poor health — but scientists have now studied the impact on mice who carry ApoE4, a genetic variant known as ‘the Alzheimer’s gene.’ APOE is a gene that codes for a protein which binds fats and cholesterol to transport them to certain systems in the body, including the brain. Carriers of ApoE4 are known to have a higher chance of developing Alzheimer’s disease in their lifetimes than those who carry other variants of APOE — and yet, there are many people with the gene variant that still manage not to get Alzheimer’s disease. Scientists at University of Southern California wanted to explore whether lifestyle factors, like diet, could offset genetic risk for Alzheimer’s.
What they found in a 2016 mouse study was that yes, lifestyle changes did appear to reduce the risk of developing Alzheimer’s, even for this higher-risk group.
During the 12-week study period, genetically predisposed mice who carried the APOE4 gene variant, and mice with the lower-risk APOE3 variant, were fed both high fat and high sugar diets. Meanwhile, groups of mice with each of these gene variants were given a healthier diet, with less saturated fat and sugar.
What the researchers found was that, on the unhealthy diet, both the mice with the high-risk ApoE4 and those with low-risk ApoE3 gained weight and became pre-diabetic. (Obesity and diabetes are both known risk factors associated with Alzheimer’s.) The breakthrough finding, the researchers reported, was that, in the unhealthy diet groups, the mice with the ‘Alzheimer’s gene’ APOE4 quickly developed the beta-amyloid plaques in their brains. This hallmark protein seen in brains with Alzheimer’s disease gets in the way of neurons, obstructing cognition and memory and eventually leading to the deal of brain cells.
Even though the mice on the healthy diet had APOE4, they didn’t develop these plaques in the brain during the few months of observation in the study.
Scientists still need to unravel exactly how poor diet affects the build up of the proteins in apoE4 carriers but this adds to research that shows that conditions like obesity, potentially, have a damaging effect on cognitive function.
What does the APOE4 gene mean for Alzheimer’s risk in humans?
Mouse studies don’t always translate to human results, but these APOE gene variants are associated with beta-amyloid plaques and with Alzheimer’s disease in both mice and people. In people, here’s a breakdown of how APOE and Alzheimer’s risk align: We inherit one copy of the APOE gene from each of our parents. If one of those copies is the APOE4 variant, it increases our risk of developing Alzheimer’s by an estimated 25 percent. Two copies of APOE4 increase the chances between three- and 12-fold.
This doesn’t mean that everyone with this gene will develop Alzheimer’s. And it certainly doesn’t mean people with no copies of APOE4 won’t develop Alzheimer’s. The disease is a complicated one: Researchers have pinpointed dozens of genes, in addition to APOE, that are related to Alzheimer’s risk. Some raise risk. Others can have a protective effect. How these genes interact is a mystery, and then, genetics is only one of many factors that drive risk. One third of people with Alzheimer’s have no genetic biomarkers at all.
Race is also a factor: Most of what genetic experts currently know about APOE4 is drawn from studies conducted in predominantly white populations. In some groups like American Indians, scientists have recently found that carrying this gene is not associated with an increased risk of the disease. But, for many people, one or two copies of APOE4 can be a wake-up call when it comes to brain health.
Further, studying diet in relation to Alzheimer’s risk is complicated, too — there are so many other variables that affect our brain health over the decades it takes for Alzheimer’s to form, and that makes diet hard to isolate and study accurately. More research is needed to understand how diet and genetic risk fit together. To learn more about genetic risk and Alzheimer’s, click here. To learn more about the relationship between diet and Alzheimer’s risk, click here.
