Reimagining Alzheimer’s (Part 7): Cholesterol Abnormalities May Contribute To Alzheimer’s Disease

(Posted on Saturday, December 17, 2022)

This article is the seventh installment in my series on Alzheimer’s disease. Read more about Alzheimer’s disease in part 1, part 2, part 3, part 4 , part 5, and part 6 of the series.

An Introduction to APOE4

A recent study published in Nature provides new insights into genetic predispositions to Alzheimer’s disease.

The E4 variant of the APOE gene is accepted as the predominant genetic risk factor for Alzheimer’s. Those who contain one copy of the E4 variant are three times more likely to develop Alzheimer’s, while those who contain two copies of the E4 variant are nearly ten times more likely to develop the disease. Unfortunately, while the E4 variant has been associated with Alzheimer’s for decades, it is still unclear exactly how it contributes to the debilitating biological and cognitive symptoms of Alzheimer’s.

Now, a study conducted by Tsai et al. at the Massachusetts Institute of Technology shows that those who contain the E4 variant display abnormalities in cholesterol metabolism. The MIT team suggests that the disruption of cholesterol metabolism could be a fundamental reason why those with the E4 variant are more likely to develop Alzheimer’s disease symptoms.

In my last article, I discussed Tsai et al.’s initial findings using brain tissue samples from Alzheimer’s patients. After characterizing the genetic makeup of tissue samples from thirty-two Alzheimer’s patients, Tsai et al. discovered that the E4 variant of the APOE gene was associated with abnormal cellular activity. These abnormalities particularly affected a subset of brain cells called oligodendrocytes.

Oligodendrocytes are supportive cells in the brain whose main function is to insulate neurons. Neurons send information to each other through electrical signals in the brain. Much like a wire is insulated to allow electricity to travel efficiently, neurons are wrapped with fats called myelin. These fats provide insulation and allow information in the brain to travel more quickly. Oligodendrocytes have the essential function of processing fat molecules to produce myelin for neurons.

Here, we will describe the additional experiments the MIT team conducted to study the relationship between the E4 variant, cholesterol, and oligodendrocytes.

Read the full article on Forbes.