By: Taylor Caron
Professor Yongku Cho of the Chemical and Biomolecular Engineering Department has received a research grant from the National Institute of Health, a primary Federal funding source, this past August. His research centers on engineering an antibody that could potentially elucidate the mechanism of neurotoxicity in Alzheimer’s disease.
The project, which is being led by Professor Cho, began in September with his graduate student Dan Li, and is focusing on what is known as the Tau protein. The Tau protein exists in brain tissue and is thought to result in neurodegeneration when improperly modified. According to Professor Cho, antibodies are a valuable tool in Alzheimer’s research because they are capable of recognizing these modifications, such as phosphorylation and acetylation of the Tau. However, a critical issue with many antibodies is that they bind unmodified Tau and proteins other than the desired target. This process is called cross-reactivity and can mislead research in Alzheimer’s disease. The focus of Professor Cho and his lab is to develop an antibody which will be more accurate in targeting the defective Tau alone.
“One study estimated that half of the antibodies currently sold on the market do not work as intended. A primary reason for this is cross-reactivity,” Professor Cho said.
Professor Cho’s project is entitled Early Detection of Tau Acetylation Using Ultra-High Affinity Antibodies. There are two primary functions to determine an antibody’s effectiveness: affinity and specificity. Affinity refers to the strength with which an antibody attracts other proteins, and specificity refers to an antibody’s ability so single out an individual protein like the Tau, without cross-reactivity. Professor Cho said much attention has been placed on affinity to the neglect of specificity, but that his project will focus on both.
“The proposal is about affinity and specificity, but I believe it is essential to develop a high-quality antibody that can both isolate the Tau and sufficiently attract it. Affinity and specificity go hand in hand,” he said.
Professor Cho spoke about what the Tau looks like under a harmful modification called acetylation, and how the grant from NIH will help him and his team detect it with high sensitivity, allowing to better elucidate its effect on Alzheimer’s disease.
“The Tau protein forms a tangle inside the brain that is a hallmark of Alzheimer’s disease,” Professor Cho said. “There are many forms or modifications of the protein, and one is known as acetylation which we believe may be the cause of the neurotoxicity.”
Professor Cho and his lab will be working with Dr. Benjamin Wolozin from Boston University to test their antibodies on human tissue samples. He is hopeful that this antibody could someday be used in detecting the early signs of Alzheimer’s disease, and enable the development of therapeutics.