With a five-year award of $ 5.5 million from the National Institutes of Health (NIH), researchers at Case Western Reserve University will seek to set up new diagnostic tests for dementia with Lewy bodies and Parkinson’s disease dementia – along with the second most common dementia after Alzheimer’s disease.
Establishing rapid and reliable testing methods for these neurological conditions, using tissue samples from non-traditional sources, such as the skin, nasal mucosa, or colon, could allow doctors to diagnose patients earlier and more easily.
Researchers will use real-time flickering-induced conversion (RT-QuIC), a relatively new technology developed in Japan, to refine the identification of telltale protein deposits in areas of the body outside of where disturbances develop. in the brain.
The findings could ultimately help doctors monitor the levels and distribution of proteins – known as alpha-synuclein, or “Lewy bodies” – across tissue sites during the different stages of these dementias, as well as their own correlation with symptoms.
“The potential of using tissues outside the brain to assess brain disorders is highly innovative,” said Shu Chen, associate professor of pathology and neurology at the Case Western Reserve School of Medicine. “Validation of this method could have huge implications for more definitive diagnoses, monitoring of disease progression, and ultimately developing potential therapies for patients.”
Allison Kraus, assistant professor in the pathology department of the medical school and specialist in neurodegenerative diseases, will serve as the project’s co-principal investigator alongside Chen, a neurobiologist and researcher on Parkinson’s disease.
The two diseases are caused by the accumulation of Lewy bodies in the nerve cells of the brain regions associated with memory, thinking and other mental abilities; patients may also develop tremors, loss of movement, and other physical symptoms.
While the clinical procedures for collecting these biological samples – such as small skin punches, nasal swabs, and colon biopsies – are well established, Chen, Kraus and colleagues will seek to develop high levels of diagnostic accuracy for each tissue source.
“Identifying where and when neurodegenerative proteins occur outside the brain will help not only with the patient’s diagnosis, but potentially their prognosis as well,” Kraus said. “Being able to have ultra-sensitive measurements of disease-specific proteins in peripheral body tissues as specific and accessible biomarkers is an exciting step towards diagnosing, treating and developing therapies for these diseases.”
The medical community has long noted the presence of some initial symptoms in patients who appear before dementia develops, including loss of smell and constipation. In recent years, researchers have linked these dysfunctions to alpha-synuclein deposits. RT-QuIC technology has made identifying such deposits easier and more efficient.
Lewy body dementia is often confused with other forms of dementia, such as Alzheimer’s, which is characterized by an accumulation in the brain of a different protein – known as tau – said Kraus, who is also developing specific tau markers using RT. – QuIC technology.
“The condition is often misdiagnosed or underdiagnosed throughout life,” he said. “We are trying to differentiate Lewy body dementia from Alzheimer’s disease and other types of dementia, which could potentially improve patient care.”
The award is jointly funded by two divisions of the NIH: the National Institute on Aging and the National Institute of Neurological Disorders and Stroke.
Scientists from Cleveland Medical Center university hospitals, Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, NIH Rocky Mountain Laboratories and three European institutions are also part of the team.
- Steven Gunzler, Brian Appleby and Curtis Tatsuoka, of the Department of Neurology, Cleveland Medical Center University Hospitals and Case Western Reserve University School of Medicine;
- Xiongwei Zhu, of the Department of Pathology, Case Western Reserve University School of Medicine;
- Clifford Harding, of the Department of Pathology, Case Western Reserve University School of Medicine and Diagnostic Institute, Cleveland Medical Center University Hospitals;
- Linda Cummings, Minh Lam, and Fabio Cominelli of the Cleveland Digestive Diseases Research Core Center (DDRCC), Cleveland Medical Center University Hospital, and Case Western Reserve University School of Medicine;
- Marwan Sabbagh, Zoltan Mari and Jiong Shi, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas;
- Byron Caughey, of NIH / NIAID Rocky Mountain Laboratories, Hamilton, Montana;
- Gianluigi Zanusso, of the University of Verona in Italy;
- Kathrin Doppler, of the University of Wurzburg in Germany; is
- Fabio Moda, from IRCCS C. Besta Neurological Institute in Italy.
This project is supported by NIH grant award R01 NS118760.
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