Alzheimer’s and APOE genotype

One very important gene that has been extremely well researched for Alzheimer’s disease is the APOE gene. This gene 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.

Late-onset Alzheimer’s disease (after age 60) is thought to be influenced both by genes and by environmental factors. So keep in mind when looking at your genetic risk that your genes are only one part of the equation when it comes to Alzheimer’s .

Knowing your risk can help you to understand the importance of doing all that you can to prevent Alzheimer’s disease.

APOE Variants:

Your APOE type is defined as combinations 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 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.

Determining APOE Variants from 23andMe Data:

To determine your APOE type from your 23andMe data or another source, you will need to look at the following two rs id’s: rs429358 and rs7412.

AncestryDNA data should not be used for determining APOE type. There is a known error in the APOE gene data for certain years of data. [ref]

APOE Allele rs429358 rs7412 Risk of Alzheimer’s
ε2/ε2 T/T T/T lower risk
ε2/ε3 T/T C/T lower risk
ε2/ε4 C/T C/T slightly higher risk than normal
ε3/ε3 T/T C/C normal risk
ε3/ε4 C/T C/C higher than normal risk
ε4/ε4 C/C C/C highest risk[ref]

Help! I don’t understand this chart (video explanation).

Again, your genetic risk isn’t the only factor involved in getting Alzheimer’s Disease.  Some people who have the highest risk factors will never get the disease.

Environmental factors play a role, and other genes could add to or decrease your risk. Check out my article on genetic mutations that decrease the risk of Alzheimer’s.

There are also other genes that add a little bit to your risk for Alzheimer’s and rare mutations found in a small percentage of the population that significantly increase risk.

Thus, your APOE type isn’t the complete picture, but it is (by far!) the biggest genetic risk factor for Alzheimer’s disease.


If you are at an increased risk of Alzheimer’s, the key is to use this knowledge to do all that you can to decrease your risk.

Below are a few of the studies that I’ve read through on the topic. This is not an exhaustive list by any means, and I highly encourage you to keep up to date with current information on the topic.

Alzheimer’s Prevention: Circadian Rhythms, Sleep, and Melatonin

Number one on my list for preventing Alzheimer’s is to block blue light at night with some nerdy-looking orange glasses. This helps to boost melatonin and increases my sleep quality.

Many have found a link between sleep quality and the risk of dementia or Alzheimer’s.[ref] Our natural circadian rhythm causes melatonin to rise in the evening and stay elevated until morning. Light in the shorter, blue wavelengths signals through receptors in our eyes to turn off melatonin production in the morning. Our modern reliance on lights at night, especially from TVs and phones, is disrupting the natural circadian rhythms.

Blue-blocking glasses, worn in the evening for several hours before bed, have been shown to increase natural melatonin production by about 50% in just two weeks. [ref]

Research studies show a strong connection between circadian rhythm disruption, melatonin, insulin regulation, and healthy brain aging.[ref][ref][ref]

Trials are also evaluating the use of melatonin supplements for Alzheimer’s. [ref]

Read more about Light at Night and Alzheimer’s Risk

Alzheimer’s Prevention: Lifestyle changes

Staying active, eating well, and keeping your blood pressure low should lower your risk of Alzheimer’s. [ref]

Inflammation in the brain is thought to be one contributor to Alzheimer’s pathology.  Several studies show that both aspirin and non-aspirin NSAID use reduced the risk of Alzheimer’s Disease.  Keep in mind that these are population-wide studies that don’t take into account genetic differences; you also need to weigh the risk of liver damage from long-term NSAID usage. [ref] [ref][ref]  Check your CYP2C9 and CYP2C8 genes also. These enzymes are involved in the metabolism of some NSAIDs, such as ibuprofen.

Cardiovascular Health:
There have been several studies that link cardiovascular health markers to the risk of Alzheimer’s. One study showed an elevated homocysteine level is associated with a higher risk of Alzheimer’s. [ref]

MTHFR and homocysteine:
Homocysteine levels are often genetically related to your MTHFR genes, methylation, and your B2, B6, and B12 levels. Overall, though, carrying the MTHFR variant doesn’t seem to be a risk factor for Alzheimer’s unless homocysteine is high. Test your homocysteine level to know if it is high.

Decrease Alcohol Consumption in late life with APOE ε4
A 2014 study found that for older adults who carry the APOE ε4 polymorphism, light to moderate drinking increased their risk for cognitive decline. From the study: “Light and moderate alcohol consumption during late life were associated with greater decline in learning and memory among APOE ε4 carriers, whereas light and moderate alcohol consumption were associated with an increase in learning and memory among non-APOE ε4 carriers. There was not a significant interaction between midlife alcohol consumption status and APOE ε4 on the trajectory of learning and memory.[ref]

Focus on Liver health:
Check out all the ways that the liver and bile acids are important in Alzheimer’s prevention on Longevity Lifehacks.

Supplements that may help in Alzheimer’s prevention

There have been lots of studies on antioxidants and Alzheimer’s disease; unfortunately, most are contradictory or inconclusive. Eating a healthy diet is, of course, essential for brain health.

Luteolin, a flavonoid found in fruits and vegetables, has been studied recently with interesting potential as far as Alzheimer’s via reducing neuroinflammation.[refRead more about luteolin on Longevity Lifehacks.

Lithium Orotate:
One mineral that has been tied to a reduced risk of Alzheimer’s is lithium. Lithium is naturally found in food sources; most people consume to be between 0.1 and 3 mg/day from food. Lithium can be purchased as a mineral supplement in 5 mg doses. (Note, this is much, much lower doses than is used in the lithium carbonate prescription medication for bipolar disorder.)

Epidemiological studies show that higher lithium levels in the drinking water may help to protect against dementia. A clinical trial showed that low doses of lithium helped AD patients to have no decrease in cognitive impairment over 15 months. [ref]  There are interactions between lithium and several prescription drugs, so always check before starting any supplement. Here is another source that looks at several studies on lithium.   Read more about lithium for Alzheimer’s and mood.

Related Genes 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 for 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. This is a touchy subject for some people, so please think it through before you check to see your APOE type.

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.


Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.