Mutations in the thyroid gene may increase the risk of developing Alzheimer’s disease in African Americans.

According to a study conducted by researchers from Rush University Medical Center, African Americans with a common genetic mutation are at higher risk of developing Alzheimer’s disease, while Europeans with the same mutation are not. The results were published in the online issue of the Journal of Clinical Endocrinology and Metabolism dated 02/22/2018.

A genetic mutation known as Thr92Alad2 polymorphism affects genes involved in the activation of thyroid hormones and is commonly found; almost half of the population is a carrier of this polymorphism. The study found that African Americans with this polymorphism were 30 percent more likely to develop Alzheimer’s dementia than African Americans without genetic polymorphism. On the other hand, in European Americans, this gene was not associated with an increased risk of Alzheimer’s disease.It’s a wonderful juxtaposition.

“This correlation is only apparent in African Americans. We have some ideas, but we don’t know why,” said Elizabeth McAninch, MD, author of the study and associate professor of endocrine metabolism at Rush.

Discovery is twist in research that began with thyroid gland

This discovery is the latest twist in a study that began several years ago in Rush’s Department of Endocrinology under the direction of Dr. Antonio Bianco, a thyroid specialist and current director of research, endocrinologists provide care for hormonal imbalances that cause health problems.

The polymorphism of Thr92Alad2 affects enzymes that activate thyroid hormones. Most often, this condition can be controlled with the standard treatment of hypothyroidism with a drug called Levothyroxine, when this enzyme treats patients with a condition known as hypothyroidism, which occurs when the thyroid hormone produced by the thyroid gland is deficient. But about 15% of patients who received Levothyroxine consistently said that it did not help them feel better.

Wondering what might be behind these reports, Makaninch and Rush’s colleagues had previously obtained brain tissue from the University of Miami brain bank from a young, healthy, deceased white male organ donor whose thyroid problems were not known at the time of death, and analyzed it to find a clue. Surprisingly, the brains of healthy donors with polymorphisms showed biomarkers that are known to play a role in neurodegenerative brain diseases.

“It was a shock to us and deserved a more thorough investigation,” recalled Makaninch.

Researchers then drew on data from long-term studies of Alzheimer’s

Endocrinologist then, with the help of Rush researchers specializing in brain aging, the extended team was assigned to work with data from three long-term group studies conducted at Rush in 1993-2012 – the Chicago Health and Aging Project (CHAP), the Religious Imperative Research (ROS) and Rush Memory Research and the Aging Project (MAP). I set it up as follows.

The CHAP cohort included 3,656 participants, of whom 2,321 were African American, who took cognitive tests for 18 years over a 3-year cycle. There were 1,707 European-American participants with no known signs of dementia who were screened annually in ROS and MAP.

Again, McAninch and his colleagues also continued to collaborate with the University of Miami Brain Bank to obtain and study brain tissue from brain donors of young and healthy African Americans.

“That’s when we saw this big discrepancy in the risk of developing dementia in Alzheimer’s disease,” says Makaninch, “and this unique result of racial stratification obtained by using CHAP data with participants of both African American and European descent mixed up on its own.”

For future research, this question should be answered

Minorities tend to be underestimated in medical research, especially African Americans when assessing the risk of developing Alzheimer’s disease. “The strength of this study was the amazing results we got in these three cohort studies at Rush, which allowed us to see the difference between African Americans and Europeans. “We’re supposed to be in the right place,” she says.

The rush-led team is already planning the next study, says Makaninch, “trying to understand why African Americans are at risk and Europeans are not.”