ApoE4 - The Alzheimer's Gene
What is the APOE gene?
ApoE is short for Apolipoprotein Epislon (ε). ApoE is a protein used for lipid and cholesterol transport in the brain, and the APOE gene is the part of the DNA that holds the code for cells to make the ApoE protein as necessary.
The APOE gene has received a lot of attention due to a large amount of published research that shows that the APOE4 variant significantly increases the risk of Alzheimer’s disease, independent of all other factors. This means that if everyone lived the same life and ate the same food, the person with the APOE4 gene would have the higher risk of Alzheimer’s disease, whereas the person with the APOE2 gene would have the lower risk of Alzheimer’s.
So how much more risk are we talking about? To understand this, let’s understand the basics of the ApoE gene.
The ApoE gene has 3 different allele possibilities: E2, E3 and E4. An allele is a copy of a gene that you receive from one of your parents. So for every gene that we have, we have 2 alleles for that gene, one from your biological father and the other from your biological mother.
This means that there are 6 different combinations that any person could end up with (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4), and each combination has a different average risk for Alzheimer’s. The E2 allele, which is protective, has a worldwide frequency of 8.4%, whereas E4 which increases Alzheimer’s risk has a worldwide frequency of 13.7%. The E3 allele is the most common with a worldwide frequency of 77.9% [1].
The table below shows the risk of Alzheimer’s based on APOE variant [1]:
However, it’s not so plain and simple though. Unfortunately the risk from APOE4 is not uniform, and differences exist across race.
For example, if you are an Indian (Asian) with APOE2/E4, your odds of getting Alzheimer’s disease are almost 2 times higher than a Hispanic with APOE4/E4 genes [1,2,3,4].
And if you’re a Japanese with APOE4/E4, you have 15 times higher risk of Alzheimer’s than a Hispanic with APOE4/E4 has [1].
And of course these are just statistics. You as an individual will have your own risks depending on multiple factors including other genes, diet and lifestyle, as well as exposure to the root causes of Alzheimer’s disease.
To learn more about the other genes associated with Alzheimer’s disease, watch our Youtube video explainer. To learn more about the root causes of Alzheimer’s disease, join our Intro Course.
I have the ApoE4 Gene. Am I Doomed?
Ok fine, you get the risk. Now can you do something about this risk?
Yes absolutely!
In a 10-year study of 29,000 individuals over the age of 60, people with double copies of the APOE4 gene living a healthy lifestyle, have significantly better outcomes than those with a better gene profile but bad lifestyle [5]. And what does a healthy lifestyle here mean? In the study, it was defined as not smoking, not drinking, eating a healthy diet, having social contact and stimulating your brain.
This research also implies that if you received a copy of E3 from each of your parents (i.e. you’re supposed to have average risk for Alzheimer’s), you can STILL have a higher than average chance of getting Alzheimer’s if you live an unhealthy lifestyle.
And if you’re still not convinced, another research study found that just 20 weeks of intensive lifestyle changes was enough to significantly improve cognition and function in Alzheimer’s patients [6].
So are you convinced now, that you can do something about your risk of Alzheimer’s disease, and not be doomed by what you inherit?
The reality is that you are NOT just your genes. This is particularly the case in diseases whose onset is post 50 years old, such as Alzheimer’s. Just because you inherited certain genes that predispose you to disease does not mean that you will definitely get the disease. It does mean that you have to work harder and smarter than others to prevent it from occurring.
Join us to learn how to adopt the healthy lifestyle that helps you reverse Alzheimer’s.
To learn more about the other genes that influence Alzheimer’s risk, join our Intro Course on the root causes of Alzheimer’s.
To learn how to reverse Alzheimer’s by adopting a healthy lifestyle and targeting the root causes of the disease, take our MASTERCLASS.
References:
[1] Liu CC, Liu CC, et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb;9(2):106-18.
[2] Farrer LA, Cupples LA, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997 Oct 22-29;278(16):1349-56.
[3] Chen Q, Wang T, et al. Protective effect of apolipoprotein E epsilon 3 on sporadic Alzheimer’s disease in the Chinese population: a meta-analysis. Sci Rep. 2022 Aug 10;12(1):13620.
[4] Agarwal R, Tripathi CB. Association of apolipoprotein E genetic variation in Alzheimer’s disease in Indian population: a meta-analysis. Am J Alzheimers Dis Other Demen. 2014 Nov;29(7):575-82.
[5] Jia J, Zhao T, et al. Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ. 2023 Jan 25;380:e072691.
[6] Ornish D, Madison C, et al. Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial. Alzheimers Res Ther. 2024 Jun 7;16(1):122.
Keywords: ApoE4, Alzheimer’s genes, Alzheimer’s disease, reverse Alzheimer’s, Bredesen Protocol, root causes of Alzheimer’s.
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