Yeast Model As Alzheimer's Test

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A U.S. scientist has developed a research tool that might provide a means of treating the earliest stage of Alzheimer`s disease.
Alzheimer`s disease is characterized by the formation of plaques in the brain largely composed of fibers made from a peptide called beta-amyloid, or A-beta. While earlier research suggested A-beta fiber caused Alzheimer`s, recent research points at much smaller aggregates of the peptide as the culprit.

'We`ve developed a yeast model system in which A-beta small aggregate formation can be detected,' said University of Illinois-Chicago Professor Susan Liebman. 'The system employs a fusion of the human A-beta peptide to a functional yeast protein, called a reporter protein, which is only active in allowing cells to grow on test media if the fusion does not form aggregates.' "One promising, emerging approach for treatment of Alzheimer's disease is to prevent these smaller aggregates from forming," said Liebman. "Disruption of these small aggregates rather than the larger fibers seems prudent since inhibition of A-beta fiber formation might cause the smaller aggregate species to accumulate, and since inhibiting smaller aggregate formation should also prevent the initial formation of the fibers."

Liebman said the yeast model system can be used to develop a high throughput assay to screen small molecules to find those that inhibit the A-beta dependent aggregation. Once that is perfected, animal and human trials would follow.

The findings were reported in BMC Biology. It was the journal's most viewed article this past month. UIC graduate student Sviatoslav Bagriantsev worked on the project in Liebman's laboratory and co-authored the paper.