APOE is a gene located on chromosome 19 that has three alleles: ApoE2, ApoE3, and ApoE4. What many people don’t know is that their APOE genotype drastically alters their risk of developing Alzheimer’s Disease (AD).
Having two copies of APOE2 reduces a person’s likelihood of developing AD by nearly 50%. Having two copies of APOE3 has a neutral effect on an individual’s risk of developing AD. Having two copies of APOE4, however, increases a person’s likelihood of developing AD by 12-15 fold, and approximately 3-5% of the world’s population has this genotype.
It’s important to note that these risk factors are associated with the average American diet and may vary in other countries.
APOE contains the instructions to make apolipoprotein, a 299-amino-acid sequence. When comparing the structure of ApoE3 and ApoE4, the two proteins differ by a single amino acid: APOE4 has an arginine residue at position 112, whereas APOE3 has a cysteine residue at this position. This single base pair change can increase a person’s chance of developing AD by 12-15 fold.
With the rise of genetic testing, many individuals can now find out their APOE genotype. Chris Hemsworth, the famous actor who plays Thor, recently discovered that he has two copies of APOE4, which likely increases his chances of developing Alzheimer’s later in life. Unfortunately, people like Hemsworth cannot do much to change their chances of developing this disease. In fact, many doctors and companies won’t inform a patient of their APOE genotype to avoid causing unnecessary worry since there is currently no cure for individuals with the E4/E4 genotype.
The field of preventive neurology has emerged, aiming to research and develop treatments for people before they develop the illness. In this light, APOE has potential as a major therapeutic target. Emerging advances in gene therapy and CRISPR have opened possibilities to modify APOE and potentially reverse the changes in carriers of E4. Additionally, biomarker development has brought the prospect of drug development for high-risk individuals.
As research continues, it’s important for individuals, healthcare providers, and policymakers to stay informed about the evolving landscape of genetic insights and therapeutic advancements, ensuring that those at risk receive the support and resources they need to navigate their health journey.