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MIT Researchers Manipulated Stem Cells to Better Understand the Role of ApoE4 in Alzheimer’s

Genetic research has played a vital role in our understanding of Alzheimer’s. Certain genetic mutations, for instance, have been identified with early-onset Alzheimer’s, helping individuals better assess their overall risk. There are also specific genes, such as ApoE4, which are known to increase one’s risk.

This area of research is critical and today, neuroscientists are beginning to understand why some people with specific genes display a higher risk of late-onset Alzheimer’s.

Scientists Discover Why People with the Gene Variant ApoE4 Display a Higher Alzheimer’s Risk

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The gene variant, ApoE4, is known to increase one’s risk of Alzheimer’s. However, until recently, researchers did not fully understand why. Since this gene is typically associated with the transportation of fatty molecules and metabolism, scientists wanted to learn more about its influence on Alzheimer’s risk.

MIT scientists conducted a study on both ApoE4 and ApoE3. There is also a third variant of this gene, known as ApoE2 (which is the rarest form and is believed to reduce your risk of Alzheimer’s). ApoE3 is the most common and does not appear to influence risk, whereas APOE4 increases overall risk.

While studying the two variants, the researchers found that ApoE4 assists in the gathering of amyloid-beta. These proteins then cause plaques in the brain — a hallmark symptom of Alzheimer’s. Upon discovering this link, the researchers successfully edited the ApoE4 gene variant, turning it into the ApoE3 variant.

Since the ApoE gene binds to lipids and cholesterol, it allows cells to better absorb lipids. In the human brain, lipids are produced by specialized cells known to astrocytes. ApoE then helps neurons to take up these lipids, supporting tasks as signaling and energy storage.

As stated in this MIT News article, only around 8 percent of the general population is believed to have ApoE2, 78 percent are said to have ApoE3, and 14 percent have ApoE4. However, these rates significantly change among those with late-onset Alzheimer’s. Of those living with this disease, thirty-seven percent carry the variant APoE4.

This means that by far, the gene variant APoE4 yields the most significant risk for late-onset Alzheimer’s. Once again, this led to the question of why some people with the ApoE4 gene have higher levels of beta-amyloid.

Using Stem Cells to Better Understand APoE4

The MIT researchers used stem cells to produce three types of brain cells, including astrocytes, neurons, and microglia. Using a gene-editing system, the researchers then converted APoE3 to ApoE4. Since everything else was identical, the researchers could see that in neurons, the expression of ApoE3 and ApoE4 differed in regards to hundreds of genes.

When cells expressed ApoE4, around 250 genes went down while 190 went up. In microglia, this level of activity was even more dramatic (over 1,100 genes showcased a reduction in activity, while approximately 300 became more active). In turn, these changes resulted in lower performance levels in cells that are supposed to remove foreign matter.

These findings suggest that if gene-editing technology becomes available to humans, it may become possible to treat patients carrying the ApoE4 gene. In theory, and based on what the researchers observed in this study, if scientists can convert ApoE4 to ApoE3, many of the characteristics of Alzheimer’s would be diminished.

A Support Group and Assessment Tool For ApoE4 Carriers

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If you carry one or two copies of ApoE4, you automatically face a higher risk of Alzheimer’s. In fact, those who carry one copy triple their likelihood of developing late-onset Alzheimer’s, whereas two copies will increase your risk twelvefold.

Of those carrying at least one copy of this gene variant, the research is still unclear in terms of prevention. Some are focusing on co-risk factors, such as smoking, hypertension, and diabetes; while others are implementing dietary changes, such as low-carb, high-fat diet. The same is true regarding episodic fasting.

Although all of these theories are intriguing, and in many ways promising, they have not yet been validated. Nutrition and lifestyle variables are considered to be “soft science” because individuals respond to diets differently. Due to the complexity of these variables, it is challenging to confirm a cause-and-effect relationship.

This level of uncertainty encouraged the development of ApoE4.Info — an online gene resource platform. This organization shares lifestyle tips and research insights to support those carrying the ApoE4 gene. To better assess one’s level of thinking, the BrainTest® app is also a helpful tool. Helping to detect early warning signs of Alzheimer’s and other cognitive impairments, those carrying this gene can obtain baseline results to better track across time.

Can I Reduce My Risk?

At this time, researchers can only speculate. However, it is believed that lifestyle factors are an important place to start. Physical activity, smoking, and alcohol intake are all key variables, as well as nutrition. Foods that are rich in polyphenolic compounds and flavonoids, including tea, vegetables, and fruits, are believed to increase anti-inflammatory and antioxidant activity.

For more information on lifestyle variables, as well as known genetic risk factors, please refer to:


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