Fragment foils Alzheimer's protein

Chemists have synthesized a protein fragment that, in test-tube studies, disrupts the formation of the fiber networks suspected to be a cause of Alzheimer's disease.

In the brains of Alzheimer's patients, a protein called beta-amyloid assembles into fibers, which clump together to create networks of fibers called plaques. In the first step toward this fiber formation, the string-like proteins bind along their sub-nanometer lengths, says Robert P. Hammer of Louisiana State University in Baton Rouge. The resulting sheets of protein organize into micrometer-scale fibers.

Hammer's team focused on a set of five amino acids in the middle of the betaamyloid, which has a total length of 40 amino acids. The scientists synthesized a protein fragment, or peptide, that mimicked this set, but they tweaked certain chemical groups that normally enable beta-amyloid proteins to bind. The idea was to create a peptide that would "interrupt or change the assembly of beta-amyloid protein," says Hammer.

The researchers compared a sample of only beta-amyloid protein with a mixture of beta-amyloid protein and the peptide at equal concentrations. The samples were kept at room temperature for 4 1/2 months. Transmission-electron-microscopy images revealed fibrous structures in the pure betaamyloid sample, but the sample containing the peptide showed no fibers, the team reports in an upcoming Journal of the American Chemical Society.--A.C.