The APOE4 gene is the most powerful genetic factor driving a person’s risk for developing late-onset Alzheimer’s disease.
But scientists from Stanford Medicine have discovered a rare mutation that actually negates the Alzheimer’s risk posed by the APOE4 gene.
They found the R251G variant changes just a single amino acid in the apolipoprotein E (APOE) gene, but that simple alteration appears to neutralize the Alzheimer’s risk normally caused by APOE4.
The research is published in the journal JAMA Neurology and was conducted by Dr. Michael Greicius et al.
The first studies linking APOE4 to degenerative brain disease came out in the 1990s, but no one yet has figured out how the gene actually increases risk.
In the study, the team mined huge sets of genetic data that included more than 544,000 people.
These included gene analysis of more than 67,000 people with Alzheimer’s, 28,000 people who have an immediate family member with Alzheimer’s, and 340,000 healthy people to compare them against.
Everyone carries a version of the APOE gene, which mainly helps manage the use of cholesterol around the body. Cholesterol is important for normal cell function, as a key ingredient in cell walls.
The most common version of the gene, APOE3, doesn’t influence a person’s risk of Alzheimer’s at all. Another called APOE2 actually protects against Alzheimer’s.
And then there’s APOE4. About 25% of people with European ancestry have one copy of APOE4.
Analyzing all that genetic data, the researchers found that the R251G variant appeared to reduce the Alzheimer’s risk of people who had inherited APOE4.
The research team also looked at a second protective mutation that reduces Alzheimer’s risk by about 60%, the study reports.
That variant, called V236E, is co-inherited with the common APOE3 gene, and provides a level of protection similar to that of APOE2.
The team says if they can better understand how the mutations are mitigating risk, this may open the door to possible treatment targets and/or biology to target for therapy development.
If you care about brain health, please read studies about how to eat your way to a healthy brain, and how to prevent brain aging effectively.
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