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 say in Neurobiology of Aging. An estimated 25 percent of the population has the XmnI polymorphism.

The study, available online but not yet scheduled for print, also showed that beta amyloid peptide, a major culprit in Alzheimer's, has an affinity for adult hemoglobin, says Dr. William D. Hill, neuroscientist at the Medical College of Georgia and Veterans Affairs Medical Center in Augusta 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, says Dr. Hill. In this case, a library of brain molecules was inserted into the virus' whiskers to find proteins that would stick to beta amyloid.

Hemoglobin, found in red blood cells and responsible for carrying 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 MCG hemoglobin experts Drs. Abdullah and Ferdane Kutlar decide
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
8-Jan-2007