Alzheimer’s and APOE type

Alzheimer's DiseaseOne very important gene that has been researched in association with Alzheimer’s disease is the APOE gene.    Late-onset (after age 60) Alzheimer’s disease 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!).  But knowing your risk can help you to understand the importance of doing all that you can to prevent AD.

The APOE  (apolipoprotein E ) gene is involved in carrying cholesterol and other fats in your bloodstream.  This gene has been studied extensively in relation to risk of Alzheimer’s Disease. Your APOE type is based on different alleles, and you will have one APOE allele from each parent.

From the NIH website:
APOE ε2 is relatively rare and may provide some protection against the disease. If Alzheimer’s disease occurs in a person with this allele, it develops later in life than it would in someone with the APOE ε4 gene.

APOE ε3, the most common allele, is believed to play a neutral role in the disease—neither decreasing nor increasing risk.

APOE ε4 is present in about 10 to 15 percent of the population and in about 40 percent of all people with late-onset Alzheimer’s. People who develop Alzheimer’s are more likely to have an APOE ε4 allele than people who do not develop the disease.

To determine your APOE type from your SNP’s, you will need to look at the following  id’s: rs429358 and rs7412.  From those results, take the first letter of each one to compute your result from one parent, and then take the second letter to compute the second result. Here is a handy chart of the combinations.  (SNP link in the table below will take you to your 23andMe results.)

APOE Allele rs429358 rs7412 Risk of Alzheimer’s
ε2/ε2 TT TT lower than normal
ε2/ε3 TT CT lower than normal
ε2/ε4 CT CT slightly higher than normal
ε3/ε3 TT CC normal
ε3/ε4 CT CC higher than normal
ε4/ε4 CC CC highest risk

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

A 2014 study found in those with at least one APOE4 allele that women were at a higher risk than men.

Prevention of Alzheimer’s Disease:

So you are at risk for Alzheimer’s…  The key is to use this knowledge to work on preventing it.  Below are a few studies that I’ve read through.  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.

NSAID’s:

There have been several studies showing that NSAID use reduces the risk of AD.  These are population-wide studies that don’t take into account genetic differences, and you also need to weigh in the risk of liver damage from long-term NSAID usage.

Cardiovascular Health:

There have been several studies that link cardiovascular health markers to the risk of AD.  One study showed that an elevated homocysteine level is associated with higher risk of Alzheimer’s.  Homocysteine levels are often genetically related to your MTHFR genes, methylation, and your B6 and B12 levels.

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

Lifestyle

A 2014 study found that for older adults who carry the APOE e4 polymorphism, light to moderate drinking increased their risk for cognitive decline.

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.  Quite a few 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. Luteolin, along with other natural anti-inflammatories, is being studied to reduce the possible neuroinflammation associated with Alzheimer’s.[ref]

One mineral that has been recently in the news is lithium.  There have been several recent studies on the effects of lithium on Alzheimer’s.  High doses of lithium, like those for bi-polar disorder, come with side-effects and long term health risks.  One study showed that low doses of lithium helped AD patients to have no decrease in cognitive impairment over 15 months.   Lithium is naturally found in food sources with some estimating that most people consume to be between .1 and 1 mg per day.  It is available in 5mg doses as a supplement at health food stores and on the internet.  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 reading:

From the Alzheimer’s Drug Discovery Foundation, an article on APOE4 and prevention ideas that don’t work as well for APOE4 carriers: http://www.alzdiscovery.org/cognitive-vitality/what-apoe-means-for-your-health

Very interesting article on the discovery of the APOE link to Alzheimer’s and current research: http://www.nature.com/news/alzheimer-s-disease-the-forgetting-gene-1.15342

SNPedia on APOE: http://www.snpedia.com/index.php/APOE

Stanford slide show on Alzheimer’s: http://stanford.edu/class/gene210/files/projects/Gen210AlzheimersDisease.pdf

 

 

 

 

 

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