Scientists develop rapid detection technique for diagnosis of neurodegenerative diseases

In a collaborative endeavor, a team of scientists led by ECE’s Professor Sang-Hyun Oh and Professor Peter Larsen  of the Department of Veterinary and Biomedical Sciences have developed a groundbreaking diagnostic technique that will aid in faster and more accurate detection of neurodegenerative diseases. Called Nano-QuIC (Nanoparticle-enhanced Quaking Induced Conversion), the technique has the potential to provide accurate detection of diseases such as Alzheimer’s and Parkinson’s in humans, and chronic wasting disease (CWD) in animals. The study is published in Nano Letters in a paper titled  “Nanoparticle-enhanced RT-QuIC Diagnostic Assay for Misfolded Proteins.”

According to Oh, senior co-author of the paper and a Distinguished McKnight University Professor, “This paper mainly focuses on chronic wasting disease in deer, but ultimately our goal is to expand the technology for a broad spectrum of neurodegenerative diseases, Alzheimer’s and Parkinson’s being the two main targets. Our vision is to develop ultra-sensitive, powerful diagnostic techniques for a variety of neurodegenerative diseases so that we can detect biomarkers early on, perhaps allowing more time for the deployment of therapeutic agents that can slow down disease progression. We want to help improve the lives of millions of people affected by neurodegenerative diseases.”

Neurodegenerative diseases such as Alzheimer's, Parkinson's, mad cow disease, and CWD (a disease that is quickly spreading in deer across North America, Scandinavia, and South Korea) share a common feature—the buildup of misfolded proteins in the central nervous system. Detecting these misfolded proteins is crucial for understanding and diagnosing these devastating disorders. However, existing diagnostic methods like enzyme-linked immunosorbent assay and immunohistochemistry can be expensive, time-consuming, and limiting in terms of antibody specificity.

The new method, Nano-QuIC, is a significant improvement over the performance of the traditional real-time quake-induced conversion  (RT-QuIC) method developed at the NIH Rocky Mountain Laboratories. Leveraging the misfolded protein’s ability to induce misfolding in normal proteins, the RT-QuIC method involves shaking a mixture of normal proteins with a small amount of misfolded protein to trigger a chain reaction that causes the proteins to multiply. The process allows for the detection of these irregular proteins. University scientists added 50-nanometer silica nanoparticles to RT-QuIC experiments and found that it dramatically reduces detection times from about 14 hours to only four hours and increases the sensitivity by a factor of 10. 

A typical 14-hour detection cycle means that a lab technician can run only one test per normal working day. However, with a detection time of less than four hours using Nano-QuIC, researchers can now run three or even four tests per day. Having a quicker detection method is particularly important for understanding and controlling transmission of CWD, a disease that is spreading in deer across North America, Scandinavia, and South Korea. The researchers believe that Nano-QuIC could eventually prove useful for detecting protein-misfolding diseases in humans, specifically Parkinson's, Creutzfeldt-Jakob Disease, Alzheimer's, and ALS.

Read more about the detection technique and its impact at the College of Science and Engineering website. 

The research was funded by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Legislative-Citizen Commission on Minnesota Resources (LCCMR), the Minnesota Agricultural Experiment Station Rapid Agricultural Response Fund, and the Minnesota Agricultural, Research, Education, Extension and Technology Transfer (AGREETT) program.

Larsen and Oh lead the University’s Minnesota Center for Prion Research and Outreach (MNPRO) molecular diagnostic research and development team, which leverages this government funding to conduct research on protein misfolding diseases that greatly impact the state of Minnesota.

In addition to Oh and Larsen, the team involved in this paper include researchers Peter Christenson (lead author and Ph.D. candidate in the Department of Electrical and Computer Engineering), Manci Li (Ph.D. candidate in the Comparative and Molecular Biosciences Program), and Gage Rowden (researcher in the Department of Veterinary and Biomedical Sciences).

Read the full paper, “Nanoparticle-enhanced RT-QuIC Diagnostic Assay for Misfolded Proteins” on the Nano Letters website.