Scientists at the University of Minnesota have developed a nanoparticle-based test that significantly improves the detection of misfolded proteins that could allow for the rapid diagnosis of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. The researchers report their findings in the American Chemical Society’s journal Nano Letters, detailing the new method, dubbed Nano-QuIC (Nanoparticle-enhanced Quaking-Induced Conversion), which was tested to detect chronic wasting disease (CWD) in deer.
Neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Bovine Spongiform Encephalopathy (mad cow disease) and CWD share the common feature of a buildup of misfolded proteins in the central nervous system. Current detection methods used for diagnosis such as enzyme-linked immunosorbent assay and immunohistochemistry are time-consuming and limited in terms of antibody specificity. Nano-QuIC improves the performance of advanced protein-misfolding detection methods, such as the NIH Rocky Mountain Laboratories’ Real-Time Quaking-Induced Conversion (RT-QuIC) assay.
“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,” said Sang-Hyun Oh, senior co-author of the paper and a professor at the University of Minnesota Department of Electrical and Computer Engineering. “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 the disease progression.”
The new method works by shaking a mixture of normal proteins with small amounts of misfolded proteins that trigger a chain reaction causing proteins to multiply which allows for the detection of the misfolded characteristics of neurodegenerative diseases. The research used tissue samples from deer to demonstrate that adding 50-nanometer silica particles to the RT-QuIC method significantly shortened the detection time from around 14 hours to four hours and increased the test sensitivity by a factor of 10.
The quicker test can now allow lab techs the ability to run multiple tests per day as opposed to a single test with a 14-hour detection cycle and the researchers say this is important in efforts to control transmission of CWD in deer across North America, Scandinavia, and Korea. While there have been no reported cases in human, some research has suggested it might be transmissible to humans. That aside, the researchers believe the new testing method could be very useful for detecting a range of neurodegenerative diseases in humans.
“Testing for these neurodegenerative diseases in both animals and humans has been a major challenge to our society,” said Peter Larsen, senior co-author of the paper and an assistant professor at the University of Minnesota Department of Veterinary and Biomedical Sciences. “What we’re seeing now is this really exciting time when new, next-generation diagnostic tests are emerging for these diseases. The impact that our research has is that it’s greatly improving upon those next generation tests, it’s making them more sensitive, and it’s making them more accessible.”