How a Genetic Variant May Reduce Your Risk of Alzheimer’s Disease

How a Genetic Variant May Reduce Your Risk of Alzheimer’s Disease

Alzheimer’s Disease is a complicated disease that researchers are still working to unravel. At the core of this research is the pursuit to try and find ways to detect, treat, and prevent the disease. While many steps have been made, there is still a lot left to discover. Recent studies have begun to provide a new way of understanding how this disease works, leading researchers to new ways of preventing its progression – potentially extending a patient’s life.

What We Know About Alzheimer’s Disease

More than five million people across the U.S. have symptomatic Alzheimer’s disease. It impacts 1 in 10 individuals who are 65 or older. About one-third of these sufferers are older than 85. Though these numbers are significant, a more subtle sign of Alzheimer’s affects even more people – mild cognitive impairment. Half of the individuals who suffer cognitive impairment will eventually develop more severe Alzheimer’s symptoms. There are medications available that can slow the progression of cognitive decline, but there are no known medications to prevent its progression. 

While there is still a lot to discover about Alzheimer’s, researchers have recently been paying attention to one particular gene variant – ApoE4. This gene variant is found three times more frequently in Alzheimer’s patients than among those who do not have the disease. Research shows that not all ApoE4 carriers will get the disease, due to a separate gene variant that has been discovered to potentially protect individuals from the disease. This variant is known as klotho, and it could help drug developers better identify clinical trial participants and treatments that could make a substantial leap in developing ways to treat Alzheimer’s. 

What is Klotho?

Klotho is an anti-aging protein that decreases as we age. The klotho gene is associated with an increased risk of age-related diseases – and this is where Alzheimer’s comes in. 

Certain klotho levels in blood appear to reduce the risk of developing Alzheimer’s disease. In animal studies, researchers found a correlation between high levels of Klotho in blood and the animal’s lifespan. As research continues, scientists are discovering this correlation in humans as well. In their studies, researchers have found instances where the ApoE4 gene is heterozygous in certain humans. This means that there is just a single copy of the variant instead of two. In these instances, there is also shown to be an increased level of the klotho protein circulating in the blood. 

Through this information, researchers began to explore the detailed information of ApoE4 carriers both with and without symptoms of Alzheimer’s. They focused their research on a group of individuals in the same age range and ethnicity. By closely monitoring asymptomatic ApoE4 carriers over a period of time, researchers were able to track if individuals with the heterozygous klotho continued to show no signs of symptoms. 

What Researchers Found

The results of these tests have been unambiguous thus far. According to the study’s lead author, the ApoE4 carrier group that was found to have the heterozygous klotho variant instead of having two, showed a 30% reduced risk of Alzheimer’s. They also found that klotho substantially slowed progression as well as minimized the beta-amyloid burden in the brains of subjects who had yet evolved to dementia. 

What This Means

Genetic testing for klotho status among ApoE4 carriers could offer a more obvious indication of a person’s risk of developing Alzheimer’s disease. With this new knowledge, researchers can begin to focus on therapeutic targets and start to unravel the mystery behind this complex disease. 


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