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Posted on / Dr. William Strohman

The ApoE Gene Explained

The apolipoprotein E (ApoE) gene is one of the most well-studied genes in the human genome. It codes for a protein that sits on the surface of cholesterol, and plays a crucial role in lipid metabolism and transport in the body. 

People become concerned with whether or not they have the ApoE gene - and what to do if they do have this gene - as it has been linked to various health conditions, including Alzheimer's disease, cardiovascular disease, stroke, Parkinson's disease, multiple sclerosis, and traumatic brain injury. 

Research is ongoing to better understand the role of the ApoE gene in these conditions and to develop potential treatments.

The End Goal: Preventing the Development of Chronic Conditions

The end goal of genetic testing for ApoE, is to help prevent the development of the ubiquitous heart disease, stroke, and cognitive decline that sometimes leads to Alzheimer’s. 

These diseases develop over the course of an entire lifetime, but, in our 20’s, we may not think about them often. On the other hand, if we only start thinking about these risks in our 60’s and 70’s, we may be a little too late to appropriately address them, which is why it is important to understand your genetic makeup now to take control of your health well into the later years of your life.

Understanding ApoE

There is sometimes confusion between the ApoE gene and other lipoproteins (surface proteins on your cholesterol) – including ApoB and Lp(a). I’m hopeful I can add further detail to these lipoproteins and provide clarification on how to mitigate risks associated with the ApoE gene.

When you hear the term ApoE you should start to associate that with the metabolism or clearing of lipids in the brain and body that are produced primarily in the liver and the brain. Hence, its role in the maintenance of the blood-brain barrier (BBB) and repair of the brain. In addition it is key in signaling pathways to neuro-inflammation. 

Identifying Risks for ApoE

As we discussed in our previous blog post - The ApoE Gene Diet & LifeStyle - we inherit two gene copies (one from Mom and one from Dad), and there are three types of this gene (ε2, ε3, and ε4 allele).

ε2 – This variation can be considered protected from Alzheimer's, but slightly higher risk of coronary artery disease.

ε3 –This type of ApoE gene is called the ‘wild type.’ Meaning that it is the most common version of this gene, at about 60%

ε4 – This variation is the one that carries additional risk for Alzheimer's, and if you inherit both type 4s, your risk of Alzheimer's may be as high as 10-fold. This gene is like inheriting a very slow cholesterol taxi system which can lead to a dangerous buildup of dietary fats, resulting in higher inflammation and oxidative stress.

The gene codes for a protein called ApoE which is found on surfaces of cholesterol, but it's always in flux, and ways to measure concentrations of the actual ApoE protein have not been worked out yet. 

Hence, we usually consider measuring the type of ApoE gene you've inherited. There is still an expression issue with this type of measurement though. Even though you may inherit a particular gene, it doesn't necessarily mean we’re going to see penetrance, which is elevations in the blood.

So, in this specific scenario, we try to correlate the inheritance risk with other known risks such as smoking and drinking alcohol, high blood pressure, cholesterol, inflammation markers and CT scores of coronaries, and MRIs of the brain.

Other Apolipoproteins

What may be confusing is that there are also other apolipoproteins, proteins on the surface of cholesterol that signal when to update, and what tissue it is destined for. 


For example, we may have measured your ApoB – which is found on the surface of your LDL, Lp(a), VLDL, and IDL. These are all subtypes of cholesterol agents in your blood serum (remember fats have to be packaged up in the blood to get from point A to point B and since the serum is water-like – we need cholesterol to transport fat via cholesterol). 

The ApoB measurement is a direct measurement of this protein you have in your serum at any one point in time and it is highly correlated with the development of coronary heart disease, possibly even more so than measuring LDL cholesterol. 

In summary, it is a sum of your lipoproteins on the surface of your most dangerous plaque-laying cholesterol particles.


There is also another Lipoprotein - Lp(a) – that we may test for. This is basically a subtype of LDL cholesterol and if you inherit this – your risk of coronary disease is much higher. This is typically a ONE-time test – to see if you've inherited this.

Mitigating Your Risk For Chronic Disease

Luckily, there are a number of things you can do to mitigate your risk for chronic diseases (especially if you have one or two copies of ε4). 

Realizing how ApoE works and means to reduce your risk of developing early Alzheimer's and/or heart disease is worth reevaluating how you live your daily life. Here are just four effective ways to reduce your risks for chronic diseases associated with the ApoE gene.

#1: Monitoring Your Cholesterol

If you have one or two copies of ε4, you probably hyper-absorb cholesterol or have a hard time riding it in the brain. You'd want any plaque-provoking cholesterol (such as LDL) to be low - 70-100, if not less. 

And, we would aim to have higher HD's, as those are typically associated with higher amounts of exercise. 

Saturated fats can drive ApoB and LDL upwards – so you’ll want to watch saturated fats in cheese or marbled meats and try to get more omega-3 fatty acids from nuts, seeds, and fish. 

In addition, KETO-like diets typically don't react well when you have the ApoE4 gene.

#2: Reduce Smoking and Alcohol Consumption

You are likely more sensitive to the vascular damage & inflammation caused by smoking and alcohol. Stopping smoking completely can be extremely beneficial, not just when it comes to the ApoE gene. 

For alcohol, highly consider reducing alcohol consumption throughout the week – guidelines today are less than 7 drinks for females per week, and males about 7-14, however, this doesn't consider your ApoE status or any other risk factors we may talk about at your Lifescape checkup. 

If you have ApoE4, shoot for much less than the recommended guidelines, if not eliminating alcohol completely.

#3: Get Adequate Sleep

You should always aim for 6 to 8 hours of adequate sleep every night. When I say this – taking an Ambien or drinking two beers or wine may knock you out, but it's NOT effective or efficient sleep. 

Effective sleep is hitting all stages including deep sleep & R.E.M. sleep which helps rid the brain of sludge. Sleep apnea is also a huge factor here and worth investigating, especially if you have ApoE4

#4: Be Mindful of Legal Drugs

Whenever I talk about long-term brain health, we must mention common substances that are readily available in America and what impact it has on our general health. These drugs have direct implications on our sleep, recovery, and inflammation. 

Additionally, with marijuana legal in Arizona, I see patients experiment with these substances, but I don't think many people realize the effects of all of our legal drugs, such as alcohol, nicotine, caffeine, and even now marijuana including THC/CBD. 

I recommend reviewing the following videos (which I’ll soon be writing articles on as well) to truly understand the impacts of these legal drugs on our bodies:

The ApoE Gene and Lifescape

Comprehensive wellness often starts with personalized medical testing. Patients of LifeScape are encouraged to test for factors like the ApoE gene to determine best proactive measures. 

If you’re ready to work with a physician who’s proactive about your care, request a Meet & Greet to learn more about enrolling in LifeScape’s Concierge Care program

Learn more about the ApoE Gene and preventative diet & lifestyle modifications in Drs. William & Lisa Strohman's Brilliant Health video! 


Request a Meet & Greet

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