By Sean Henahan, Access Excellence

CHAMPAIGN, Ill. - A gene that is known to contribute to the progression of Alzheimer's disease also appears to play a role in song-learning in birds, according to researchers at the University of Illinois.

The gene in question encodes a protein called synelfin that is linked with devastating brain lesions known as senile plaques, a signature of Alzheimer's disease. The researchers found that the same protein is abundant in zebra finches in the parts of the brain responsible for song-learning, but then declines as the learning ceases.

"The amount of the protein appears to be correlated with song-learning activity," said David Clayton, a molecular biologist in the U. of I. cell and structural biology department. "This protein may provide a window into a very basic brain process. Our songbird studies suggest it may have a normal function to increase learning. Yet as a side effect, it also may make human brain tissue more susceptible to senile plaques."

Clayton and colleagues discovered the synelfin protein after setting out to address a long-standing question about the behavior of birds such as canaries and zebra finches: Why do most songbirds learn their songs only during a particular time of their lives? The researchers, whose work is supported by the National Institutes of Health, theorized that there may be changes in specific proteins within a key brain region known as lman.

Using recombinant DNA methods, they made a collection of probes for genes that encode songbird brain proteins. After analyzing the proteins one by one, the researchers picked synelfin to study because they found it to be turned on in the lman region of zebra finches that were learning their songs, and then abruptly turned off. The bird learns its song when it is about a month old by listening to a tutor -- usually its father. Exactly how the protein works in songbirds, or in humans, is not known.

"In humans, the distribution of synelfin is the best predictor yet of where senile plaques are most likely to develop," Clayton said. "A normal, healthy brain has few, if any, plaques; the more plaques you have, the sicker you are."

Synelfin and another protein, the amyloid precursor protein, give rise to small peptides that make up the sticky, insoluble skeleton of the senile plaque. The U. of I. researchers have found at least one other clue potentially linking synelfin to Alzheimer's disease. Synelfin resembles apolipoproteins, molecules that mediate protein activity.

Other researchers (see previous Science Update reports) have shown recently that the apolipoprotein E4, a major carrier of hydrophobic molecules in the brain, is a significant genetic risk factor for the development of Alzheimer's. Clayton speculates that synelfin may be an essential factor in plaque formation and that it may interact with different apolipoproteins to influence the likelihood of senile plaques and Alzheimer's.

The research appeared in the August, 1995 issue of the journal Neuron.