Alzheimer's antibodies

An new, easy way to target harmful proteins

Biology News – A service of Macroevolution.net

Antibodies have complex structures

The process is reported in the Dec. 5, 2011 early edition of the Proceedings of the National Academy of Sciences. The process, outlined in the paper, titled "Structure-based design of conformation- and sequence-specific antibodies against amyloid β," could be used, not only in the case of Alzheimer's, but also as a general tool to understand other complex disease pathology and develop new antibody-based drugs.

Antibodies are large proteins produced by the immune system to fight infection and disease. They are made up of a large Y-shaped protein topped with small peptide loops. These loops bind to harmful invaders in the body, such as a viruses or bacteria. Once an antibody is bound to its target, the immune system sends cells to destroy the invader. Finding the right antibody can determine the difference between death and recovery.

Scientists have long sought methods for designing antibodies to combat specific diseases, but have been unable to produce antibodies that attach only to a target specific molecule. The task has been to complex.

When trying to design an antibody, the arrangement and sequence of the antibody loops is of utmost importance. Only a very specific combination of antibody loops will bind to and neutralize each target. And with billions of different possible loop arrangements and sequences, it is seemingly impossible to predict which specific loops will bind to a specific target molecule.

But with the new antibody design process, the researchers succeeded in creating antibodies that target a particular, devastating molecule: the Alzheimer's protein. The research, which was led by Assistant Professor of Chemical and Biological Engineering Peter Tessier, uses the same molecular interactions that cause the Alzheimer's proteins to stick together and form the toxic particles that are a hallmark of the disease.

"We are actually exploiting the same protein interactions that cause the disease in the brain to mediate binding of antibodies to toxic Alzheimer's protein particles," Tessier said.

Alzheimer's disease is due to a specific protein -- the Alzheimer's protein -- sticking together to form protein particles. These particles then damage the brain. The formation of similar toxic protein particles is also central to diseases such as Parkinson's and mad cow disease.

Most significantly, the new Alzheimer's antibodies attached themselves solely to the harmful clumped proteins, and not the harmless monomers or single peptides not associated with disease.

Tessier and his colleagues say it should be possible to use their technique also to target and better understand other, similar types of protein particles in disorders such as Parkinson's disease.

"By binding to specific portions of the toxic protein, we could test hypotheses about how to prevent or reverse cellular toxicity linked to Alzheimer's disease," Tessier said.

In the long term, as scientists learn more about methods to deliver drugs into brain tissue -- which is extremely well-protected -- it should be possible to use these new antibodies to target those drugs specifically to Alzheimer's proteins, or other proteins causing disease.