Genetic Variation May Reduce Alzheimer’s Risk

Adults with a genetic variation enabling them to express higher levels of fetal hemoglobin may have a reduced risk of Alzheimer’s disease, researchers say.

A study of 209 families with at least two siblings with Alzheimer’s and one unaffected sibling showed that those with this genetic variation are less likely to have the disease, researchers said in Neurobiology of Aging. An estimated 25 percent of the population has the XmnI polymorphism.

The study also showed that beta amyloid peptide, a major culprit in Alzheimer’s, has an affinity for adult hemoglobin, said Dr. William D. Hill, a neuroscientist at MCG and Augusta’s Veterans Affairs Medical Center and a corresponding author.

The hemoglobin attraction was discovered by using phage display technology to screen thousands of molecules in the human brain to find those that interact with beta amyloid peptide. This approach uses a virus to infect a bacterium so the bacterium will copy the virus. The result looks like a microscopic cigar, with the proteins of interest as whiskers on one end. In this case, a library of brain molecules was inserted into the virus’ whiskers to find proteins that would stick to beta amyloid.

Hemoglobin, a component of red blood cells that carries oxygen in the body, was among those that stuck.

Surprised that hemoglobin was even present, Dr. Hill suspected it was an artifact of preparing brain tissue for the library. But once he saw the attraction, he could not ignore it.

His lab actually first found an attraction for fetal hemoglobin, another surprise since most adults have little of this substance that snatches oxygen from the placenta and holds onto it tightly for the fetus. Looking further, his lab found adult hemoglobin was binding as well, so Dr. Hill and Drs. Abdullah and Ferdane Kutlar decided to study the XmnI polymorphism, which can significantly increase fetal hemoglobin expression in adults. They turned to colleagues at the University of Alabama at Birmingham, one of three sites that contributed family data to the National Institute of Mental Health Alzheimer’s databank.

At the UAB databank, headed by Dr. Rodney C.P. Go, researchers found more surprises. “We wanted to look at people who had Alzheimer’s and family members who don’t to see who expressed the polymorphism the most,” said Dr. Hill. They suspected it would be the Alzheimer’s patients and found just the opposite.

In what they suspect to be a vicious cycle, beta amyloid could injure red blood cells, allowing more of them than usual to break open and spill their