A new method for studying Alzheimer’s disease that preserves the natural environment of key proteins was announced by researchers at the FAMU-FSU College of Engineering on Mar. 11. The technique, published in Protein Science, allows scientists to examine disease-causing proteins without altering their structure, which could lead to more accurate research and potential breakthroughs in treatment.
Alzheimer’s disease affects millions worldwide, and understanding its underlying mechanisms is crucial for developing effective therapies. Traditional methods for extracting proteins from brain cells often use detergents that disrupt the surrounding lipids, changing how these proteins behave and making it difficult to study them as they exist in the human brain.
Professor Ayyalusamy Ramamoorthy, a co-author of the study, said, “Alzheimer’s disease is devastating. More people are living longer, and that means more people are going to be living with Alzheimer’s disease, so we need to find a cure for it and other aging-related amyloid diseases, like Parkinson’s and Type 2 diabetes. Attempts to develop drugs for Alzheimer’s disease have failed, so we started to work on the C99 protein, which is the origin for everything.”
The research team developed a non-detergent-based polymer method to extract C99—a protein involved in Alzheimer’s progression—while preserving its lipid environment. Ramamoorthy said, “We have been developing these synthetic polymers that can extract proteins present in the cell membrane directly without using detergents. This work was about using synthetically prepared polymers in my lab to isolate a precursor protein along with the lipids present in the cell membrane and reconstituting them together in the form of disc-shaped particles called nanodiscs for a deeper medical investigation.”
C99 is produced when enzymes cut amyloid precursor protein (APP) found in the brain. The resulting fragments can accumulate with lipids and form plaques responsible for memory loss by killing neuronal cells. In this study, researchers isolated C99 from bacterial cell membranes along with its surrounding lipids using their new polymer technique and confirmed that both remained intact after extraction.
“This work provides a toolkit for studying Alzheimer’s disease at the molecular level and it lets scientists observe C99 in its ‘natural habitat,’ which is something that had not been possible in more than 30 years of research,” Ramamoorthy said. “It creates a biomedically relevant and more accurate method for preparing proteins used in therapeutic discovery and Alzheimer’s disease modeling.”
The research could help improve pharmaceutical development as well as diagnostic tools or biotechnology manufacturing related to neurodegenerative diseases. Ramamoorthy concluded: “Drug development has so far not been able to solve the problems posed by Alzheimer’s disease. Our hope is that this new method will give researchers a clearer picture of how the C99 protein works and contributes to this disease, so that we can develop ways to stop its progression. Ultimately, we can find a cure.”
Researchers from the University of Michigan also contributed to this study, which was supported by funding from the National Institutes of Health.
