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 stringlike 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 beta-amyloid, 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 beta-amyloid sample, but the sample containing the peptide showed no fibers, the team reports in the March 22 Journal of the American Chemical Society.