Life Extension Magazine®

How ApoE Testing Helps Gauge Disease Risk

A simple cheek-swab test can determine if you express the ApoE4 gene that indicates far greater risk for Alzheimer’s and heart disease.

Scientifically reviewed by: Gary Gonzalez, MD, in May 2023. Written by: Richard Edwins.

Many people worry about Alzheimer's disease.

Few know there's a simple genetic test that can tell you whether you're at increased risk of developing it.

Apolipoprotein E (ApoE) is a protein that helps carry cholesterol, fats and fat-soluble vitamins in the blood.¹ One type of ApoE helps predict one's risk for Alzheimer's dementia.

The gene that provides the instructions for making ApoE in humans has three different forms.

Studies have shown that one specific ApoE form increases risk for Alzheimer's disease^1-3 and is also associated with increased risk for cardiovascular disease.^1,3-5

Another form of the gene reduces risk for Alzheimer's disease.^1-4,6

Testing for different ApoE types is a tool that helps assess the risk of developing these conditions.

ApoE Types

The ApoE gene exists in three different forms:²

ApoE e3 is the most common type. About 60% of the population has two copies of ApoE e3, one from each parent.
ApoE e4 is less common, and it is the problematic type. About 20%-30% of people have one or two copies of this form.
ApoE e2 is the least common form. Only about 10%-20% of people carry at least one copy of this gene.

Who Should Test?

The problematic ApoE e4 form is present in approximately 25% of the U.S. population.⁹ Genetic testing for ApoE status can be done with a simple cheek swab from home.

ApoE status does not tell you if you will or will not develop Alzheimer's disease or other conditions, only whether you are at greater risk of having them.

If you are concerned about your risk of Alzheimer's or cardiovascular disease or have a family history of either, consider testing your ApoE status, the sooner the better, so preventative measures can be taken if ApoE e4 is detected.

Your physician can also discuss how you can use the test results to make lifestyle changes to minimize your overall risk.

ApoE Functions

ApoE is mainly synthesized in the liver, and it helps transport lipids, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood.

In the brain, ApoE is mainly produced by astrocytes that help transport essential lipids and maintain healthy neuronal signaling.⁷

The three forms of ApoE have different lipid-binding capacities that involve their abilities to bind or clear amyloid beta plaques that form around nerve cells.^1,8,9

ApoE genes function to help control brain inflammation,^7,9 and support removal of degenerated cell membranes and lipids that accumulate with aging.⁸

ApoE binds to LDL receptors in the liver to remove remnant lipoprotein particles (chylomicrons and VLDL) from circulation. Defects in ApoE result in an increase in plasma cholesterol and triglycerides due to impaired clearance of chylomicrons, VLDL and LDL.¹⁰

One distinct feature of Alzheimer's disease is the build-up of clumps of beta-amyloid in the brain. ApoE enhances beta-amyloid break-down, both within and between cells.

Unfortunately, the ApoE e4 genetic variant is not as effective as the others at breaking down the beta-amyloid clusters, controlling brain inflammation, and protecting brain and nerve cells.¹¹

Alzheimer's Risk

In population studies, the ApoE genetic type correlates with risk for Alzheimer's disease in the following ways:

ApoE e4: The presence of even one copy of the e4 form of the gene increases the risk of developing Alzheimer's disease.^2,3,6 Typical estimates suggest one e4 gene increases the risk of Alzheimer's disease two to three fold, whereas having two copies (one from each parent) is associated with 8 to 12 fold greater risk than average.¹²
ApoE e3: This gene form is not considered to have any impact on risk for Alzheimer's disease.
ApoE e2: The rarest form of the gene has been found to be protective, reducing risk of developing Alzheimer's disease.^1-3

A study published in 2022 found that ApoE e4 is linked to faulty cholesterol processing in the brain, which leads to defects in the protective coating around nerve fibers. That, in turn, may cause memory problems.¹³

Having the e4 gene does not mean someone will develop Alzheimer's disease. But it does mean there's an increased risk of developing it. It also means there's a greater risk of developing it at a younger age, and of having a faster decline in cognitive function as it progresses.^2,6

A genetic test can identify which form of the ApoE gene a person has. Those who discover they're at higher risk can make changes to reduce other risk factors for Alzheimer's disease.¹

Other Health Outcomes

ApoE status is associated with other health conditions.

Most notably, having the ApoE e4 gene form is associated with higher cholesterol levels and increased risk of cardiovascular diseases.^1,3,5,10 It plays a role in glucose transport, neuronal signaling, and mitochondrial function. Independently, ApoE e4 may trigger inflammatory response causing neurovascular dysfunction.⁷

Genetic testing can identify those at higher risk for these conditions, allowing them to monitor their health and make changes that could help ward off disease.

What ApoE Genetic Testing Can Tell You

Apolipoprotein E (ApoE) is a protein that helps carry lipids, fat soluble vitamins and cholesterol in the blood.
Three forms of the gene for ApoE exist in humans: e4, e3, and e2.
The ApoE e4 form is associated with an increased risk of developing Alzheimer's disease.
The rare ApoE e2 form is associated with a reduced Alzheimer's risk.
The most common form of the gene, ApoE e3, does not appear to have an impact on risk.
The ApoE e4 form is also associated with increased risk for other conditions, including cardiovascular disease.
Genetic testing can identify which form of the ApoE gene people have.
Those at higher risk for these conditions can consult with a doctor about making lifestyle changes to minimize overall risk.

Summary

Genetic testing to see which form of the apolipoprotein E (ApoE) gene you have can help assess your risk for certain chronic diseases, particularly Alzheimer's disease.

Having the ApoE e4 form of the gene is considered a risk factor for Alzheimer's and heart disease. On the other hand, possessing a copy of the e2 form indicates reduced risk of Alzheimer's disease.

Genetic testing can allow people at greatest risk for developing Alzheimer's and cardiovascular diseases to make healthy lifestyle choices to reduce the dangers.

What Dietary and Lifestyle Changes Can Be Beneficial for Alzheimer's Disease? ¹⁴

The Mediterranean diet has been linked to a reduced risk of Alzheimer's and other neurodegenerative diseases.^14-16
Aggressive dietary interventions demonstrated to be efficacious in reversing early Alzheimer's dementia include eliminating red meat, processed foods, simple sugars and excess carbohydrates while increasing intake of healthy plant foods, fiber, overnight fasting, and exercise.^17,18
Low-calorie diets have been linked to a reduced risk of cognitive decline.¹⁵
Avoiding smoking and protecting against hypertension, diabetes, dyslipidemia, and obesity, may help in the prevention of dementia.¹⁵
Regular exercise may directly benefit brain cells by increasing blood and oxygen flow in the brain.¹⁴
Limiting alcohol consumption.¹⁶
Engaging in late-life cognitive activities–being intellectually engaged by keeping the mind active–may benefit the brain.¹⁶
Supplement the brain with basic cognitive support–nutrients such as omega-3 fatty acids, curcumin, resveratrol, and magnesium.¹⁵

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

References

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Rebeck GW. The role of APOE on lipid homeostasis and inflammation in normal brains. J Lipid Res. 2017 Aug;58(8):1493-9.
Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases. Neurobiol Dis. 2014 Dec;72 Pt A:3-12.
Jiang Q, Lee CY, Mandrekar S, et al. ApoE promotes the proteolytic degradation of Abeta. Neuron. 2008 Jun 12;58(5):681-93.
Available at: https://www.uptodate.com/contents/genetics-of-alzheimer-disease?search=apoe4&source=search_result&selectedTitle=1~31&usage_type=default&display_rank=1. Accessed February, 8, 2023.
Blanchard JW, Akay LA, Davila-Velderrain J, et al. APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature. 2022 2022/11/01;611(7937):769-79.
Available at: https://www.alz.org/alzheimers-dementia/research_progress/prevention. Accessed February, 4, 2023.
Bhatti GK, Reddy AP, Reddy PH, et al. Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease. Front Aging Neurosci. 2019;11:369.
Dhana K, Evans DA, Rajan KB, et al. Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies. Neurology. 2020 Jul 28;95(4):e374-e83.
Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17.
Bredesen DE, Amos EC, Canick J, et al. Reversal of cognitive decline in Alzheimer's disease. Aging (Albany NY). 2016 Jun;8(6):1250-8.