Alzheimer’s and APOE genotype

One very important gene that has been very 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 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 (and many other diseases!).

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

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.

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

Caution: SNPedia.com warns that AncestryDNA data for rs429358 is often incorrect and should not be used for determining APOE type.

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

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


Lifehacks:

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.

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.

Quite a few studies have found a link between sleep quality and the risk of dementia or Alzheimer’s. 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. More and more research studies are showing a connection between circadian rhythm disruption, melatonin, insulin regulation, and healthy brain aging.[study][study][study] Trials are also evaluating the use of melatonin supplements for Alzheimer’s[study].

Exercise:
Additionally, staying active, eating well, and keeping your blood pressure low should lower your risk of Alzheimer’s.

NSAID’s:
There have been several studies showing 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. Two good studies to read:  Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer’s DiseaseAnti-inflammatory drugs and risk of Alzheimer’s disease: an updated systematic review and meta-analysis

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

MTHFR:
Homocysteine levels are often genetically related to your MTHFR genes, methylation, and your 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 — get your homocysteine tested so that you know if it is high.

Alcohol Consumption:
A 2014 study found that for older adults who carry the APOE e4 polymorphism, light to moderate drinking increased their risk for cognitive decline.  From the study: “Light and moderate alcohol consumption during late life was associated with greater decline in learning and memory among APOE e4 carriers, whereas light and moderate alcohol consumption was associated with an increase in learning and memory among non-APOE e4 carriers. There was not a significant interaction between midlife alcohol consumption status and APOE e4 on the trajectory of learning and memory.[ref]”

Supplements:
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, always a good idea.

Luteolin, an antioxidant flavonoid, has been studied recently with interesting potential as far as Alzheimer’s.[ref]

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 .1 and 1 mg per day from food. Lithium can be purchased as a mineral supplement (e.g. 5mg dose), or it can be prescribed by a doctor for bipolar disorder. High doses of lithium, such as prescription doses for bipolar disorder, come with side-effects and long-term health risks — along with a decreased risk of dementia.

What about low doses of lithium as a mineral supplement? One study showed that low doses of lithium helped AD patients to have no decrease in cognitive impairment over 15 months. You can buy lithium in 5 – 10 mg doses as a supplement. 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.

More to Learn:

More to read:

https://www.geneticlifehacks.com/genetic-mutations-that-protect-against-alzheimers-disease/

https://www.geneticlifehacks.com/melatonin-key-to-health-and-longevity/

 

 

 

 



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17 Comments on “Alzheimer’s and APOE genotype

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  3. If you look at the RSID, how can you tell which allele you are looking at? TT and CT both overlap between different alleles and confer different risk levels.

  4. I’ve just recently heard about the APOE gene. It’s nice to know what the risks are depending on which allele you have. Thank you for the tips to help decrease the risk of developing Alzheimer’s!

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  6. My 23&Me results show: rs7412, C to T; rs429358, T to C.
    Could you help me figure out what that means? I’m a 64 yr old female; both my father & my maternal grandmother had Alzheimer’s.

    • I’m a bit confused by what you are saying about your 23andMe results. When you log in to 23andMe and look at the raw data for rs7412, what does it say under the “Your Genotype” column?

    • Does it say C/T T/C? If so it sounds like you carry both the affected risk E4 allele and the protective E2 allele. It suggests that you might have a slightly elevated risk.

  7. Wondering why on the allele risk chart that if the E2/E3 line matches TT and CT, why does the next line indicate E2/E4 when the alleles are shown as CT and CT.
    Seems like it is reversed with the next line which is E3/E3 – which is matched with TT and CC

    • Hi Rick,
      Thanks for reading and commenting on the article.
      I’m not sure that I exactly understand what you are asking here, but let me attempt to answer what I think your question might be… E2 is represented by rs429358 T allele combined with rs7412 T allele. E4 is represented by the combo of rs429358 C allele and rs7412 C allele. So the line showing E2/E4 gives a combo of CT and CT — one T allele in each SNP and one C allele in each SNP.
      APOE E3 is determined by rs429358 T and rs7412 C. Thus the TT and CC would represent E3/E3.
      Does this answer your question?
      Debbie

  8. I’m confused. A search of my raw data shows rs7412 AC, but there is no rs429358. Can you help interpret this please.

    • Hi Tracy,
      To determine the APOE genotype, you will need the data for both rs id numbers. Is your raw data from 23andMe or AncestryDNA? rs429358 should be available from both of those companies.
      Debbie

  9. I recently found that I have the a ApoE2/4 variant. I have looked and looked and have not been able to find much on what type of diet would be best for me. I’ve read the book, “Beat the heart attack gene“ and it indicates that 2/4 is mostly like a E3/3 sine E2 is protective for AZ but E4 is an indicator for AZ.

    Can anyone help me with figuring out this 2/4 variant?

    Thanks,
    John

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