~ The APOE alleles are important in understanding your Alzheimer’s risk, and the data is found in your 23andMe raw data file (if you want to know).
~ APOE is involved in carrying cholesterol and other fats in your bloodstream, and a common variant of the gene is strongly linked to a higher risk of Alzheimer’s.[ref]
~ Alzheimer’s risk is influenced both by genes and environmental factors. Genes are only one part of the equation for Alzheimer’s.
~ Knowing your risk can help you prioritize lifestyle changes for prevention of Alzheimer’s disease.
APOE Gene Variants:
Your APOE type is defined as a combination of three different alleles (ε2, ε3, or ε4), and you will have one APOE allele from each parent.
The NIH website explains:
- APOE ε2 is not very common and is associated with a decreased risk of Alzheimer’s.
- APOE ε3 is the most common allele and neither increases nor decreases the risk of Alzheimer’s.
- APOE ε4 is found in about 15% of the population and increases the risk of Alzheimer’s disease. About 40% of people with Alzheimer’s carry this allele.
What does APOE do?
APOE plays a critical role in the metabolism and transport of cholesterol and other fats in the body, particularly in the central nervous system.
The APOE protein is primarily involved in the transport and metabolism of lipids in the blood, where it helps to carry cholesterol and other lipids to and from cells, and in the brain, where it helps to transport lipids across the blood-brain barrier.
In the brain, APOE helps to regulate the clearance of beta-amyloid protein, which is a key component of the plaques that form in the brains of people with Alzheimer’s disease. APOE is also involved in many other processes in the body, such as inflammation, immune function, and repair of tissues after injury.
In people with Alzheimer’s disease, there is reduced blood glucose uptake and energy (ATP) creation in the brain. Glucose enters the brain through glucose transporters in the blood-brain barrier. Brain glucose is tightly regulated.[ref]
The different APOE genotypes (E2, E3, E4) result in different-sized APOE molecules. Additionally, the different APOE types are associated with the level of plasma APOE.
The APOE E2 allele is linked to higher plasma APOE levels, while the APOE E4 allele is linked to lower plasma APOE levels. One study explained that “Low plasma levels of apoE are associated with increased risk of future Alzheimer’s disease and all dementia in the general population…”[ref]
Finding your APOE type from 23 and Me Data:
To determine your APOE type from your 23 and Me data or another source, you will need to look at the following two rs id’s: rs429358 and rs7412.
NOTE: AncestryDNA data should not be used for determining APOE type. There is a known error in the APOE gene data for certain years of their data files.[ref] Other data files that work with Genetic Lifehacks membership, such as 23andMe, selfdecode, sequencing.com, or MyHeritage should work fine, although rare errors are always possible.
|Risk of Alzheimer’s|
|ε2/ε4||C/T||C/T||just slightly higher risk than normal|
|ε3/ε4||C/T||C/C||higher than normal risk|
You inherit one APOE allele from your mother and one from your father. Thus, you will have two APOE allele types. There are six possible combinations (listed above): E2/E2, E2/E3, E3/E3, E3/E4, E4/E4.
The APOE E3 type is the normal and most common type. For people with two copies of APOE E3, they will have what is considered the typical risk allele for Alzheimer’s disease. For people with an APOE E4 or E2 allele, the increase or decrease in risk from other APOE types is relative to the E3 allele.
What does APOE E4 mean?
APOE E4 elevates the risk of developing Alzheimer’s disease compared to the more common version of the gene, APOE3. The APOE4 allele also increases the risk of developing the disease at a slightly younger age.
APOE2, on the other hand, can be protective against Alzheimer’s disease.
In addition to Alzheimer’s disease, APOE4 has also been linked to other brain conditions, including Lewy body dementia and TDP-43 pathology in Alzheimer’s disease. Additionally, APOE E4 carriers are at a slightly increased relative risk of stroke and cardiovascular disease.[ref][ref]
Other factors involved in Alzheimer’s:
Again, your APOE gene isn’t the only factor involved in getting Alzheimer’s Disease.
- A minority of people with the E4/E4 alleles don’t end up with Alzheimer’s.
- Environmental and lifestyle factors play a big role. (Covered in the Lifehacks for Alzheimer’s Prevention section below)
- Other genes could add to or decrease your risk. Check out my article on genetic mutations that decrease the risk of Alzheimer’s.
- Variants in the KLOTHO gene can decrease the APOE E4 elevated risk.
Other genes add a little bit to your risk for Alzheimer’s, and rare mutations found in a small percentage of the population significantly increase the risk.
Thus, your APOE type isn’t the complete picture, but research does show it to be the most significant common genetic risk factor for Alzheimer’s disease.
APOE E4 benefits:
For almost every genetic variant with a negative, there is also a tradeoff or benefit. This holds true even for the APOE E4 allele.
Protective against age-related macular degeneration:
The APOE E4 allele has been shown in several studies to protect against macular degeneration.[ref]
Visual working memory benefits at age 70:
“ε4-carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4-carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer’s disease.”[ref]
Infectious disease protection:
The APOE E4 allele is linked to a decreased risk of chronic hepatitis C and a lower risk of liver problems in people who have hepatitis C. [ref]
Lifehacks: Alzheimer’s Prevention
If you are at an increased risk for Alzheimer’s, the key is to use this knowledge to do all that you can to decrease your risk.
My top 3 list for Alzheimer’s prevention:
This is just where I’ve personally chosen to focus in the prevention of Alzheimer’s disease.
Everything in this Lifehacks section is backed by research and is likely impactful. I’ve found picking out three or four focus points is more manageable and encouraging. However, understanding the other lifestyle and supplement options is also important (and I tend to mix it up, trying to incorporate everything over the course of the year).
Related Articles and Topics:
Genetic Mutations that Protect Against Alzheimer’s Disease
Alzheimer’s disease is a scary possibility that faces many of us today — whether for ourselves or aging parents and grandparents. Currently, 10% of people aged 65 or older have Alzheimer’s disease (AD). It is a disease for which prevention needs to start decades before the symptoms appear.
Alzheimer’s and Light at Night: Taking action to prevent this disease
With the advent of consumer genetic testing from 23andMe, AncestryDNA, etc., it is now easy to know if you are at a higher risk of getting Alzheimer’s Disease (AD). Those with APOE-ε3 are at normal risk for Alzheimer’s, and those who carry an APOE-ε4 allele (or two) are at an increased risk.
TREM2 and Alzheimer’s Disease Risk:
Another important gene to check for Alzheimer’s risk is TREM2. Uncommon variants in this gene affect your brain’s immune response.
Serotonin 2A receptor variants: psychedelics, brain aging, and Alzheimer’s disease
Learn how new research on brain aging and dementia connects the serotonin 2A receptor with psychedelics, brain aging, and Alzheimer’s.
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