According to MedPage Today, carriers of the gene variation APOE4 are much more at risk of developing Alzheimer’s disease. However, researchers found that one copy of the Klotho gene mutation, KL-VS, reduced the risk, even in adults with APOE4. Read the full source studies One and Two published in JAMA Neurology.
Alzheimer’s Disease
Alzheimer’s disease is a progressive neurological disorder that causes brain cells to deteriorate and die. A combination of genetics, lifestyle choices, and environmental factors cause Alzheimer’s disease. However, research has shown that APOE4 is a major genetic risk factor. Symptoms include memory loss, pneumonia, infections, changes in personality, and difficulty with reasoning and decision-making. Read more about Alzheimer’s disease here.
Research Findings
On a global scale, only about 15% of individuals carry APOE4. Yet this variant is found in over half of patients with Alzheimer’s disease. As such, researchers have named APOE4 as a major risk factor in disease development. According to Michael Greicius, MD, MPH, having one copy of APOE4 increases the risk of Alzheimer’s by 3-4x, up to 10x with two copies.
But for some patients with APOE4, they never show any symptoms. Researchers wondered why some people with this identifying gene developed the disease and others did not.
It might have something to do with KL-VS, a variation of the Klotho gene that is linked to cognition. Every person in the world has the Klotho gene. This gene, and its resulting hormone and protein, help with anti-aging and organ function. However, only 20% of people carry the KL-VS variant. According to researchers, people with one copy of the variant have better outcomes than those with two.
The Studies
Two separate studies looked at the impact of KL-VS on patients at risk of developing Alzheimer’s disease.
The first study examined 25 independent Alzheimer’s studies, which included data from a total of 24,743 participants over the age of 60 over a period of four years.
They found that people with APOE4 and KL-VS were less at risk of losing cognitive function or developing Alzheimer’s disease. The KL-VS variant began protecting patients from this starting around age 77. Ultimately, researchers also determined that those with KL-VS also had reduced levels of amyloid beta (Aβ). Amyloid beta are peptides. In patients with Alzheimer’s, many have elevated levels of amyloid beta, which form amyloid plaques in the brain.
While the second study did not find the same link between KL-VS and amyloid beta after the age of 80, they still found that the Klotho variation could play a huge role in developing treatments for the future. For now, researchers urge doctors to consider someone’s KL-VS status when discussing the risk of Alzheimer’s development.
