Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify new biomarker for Creutzfeldt-Jakob disease, the human form of mad cow disease

10.03.2011
Case Western Reserve School of Medicine findings appear in PLoS ONE journal
Neena Singh, MD, PhD and colleagues at Case Western Reserve University School of Medicine have identified the first disease-specific biomarker for sporadic Creutzfeldt-Jakob disease (sCJD), a universally fatal, degenerative brain disease for which there is no cure. sCJD is one of the causes of dementia and typically leads to death within a year of disease onset.

The finding, published in the March 9th issue of PLoS ONE, a scientific journal produced by the Public Library of Science, provides a basis for developing a test to diagnosis sCJD while patients are still alive. Presently, the only definitive diagnostic test for the disease requires brain tissue be obtained by biopsy or after death.

In their study, Dr. Singh, associate professor of pathology at the School of Medicine, and her team found that levels of the iron-transport protein transferrin (Tf) are significantly decreased in the cerebrospinal fluid (CSF) of patients with sCJD well before the end stage of the disease, potentially allowing for earlier diagnosis.

"The decrease in Tf is significant enough to distinguish sCJD from dementia of non-CJD origin with an accuracy of 80 percent," Dr. Singh says. "When combined with the currently used non-disease-specific biomarker T-tau, the diagnostic accuracy increases to 86 percent. This suggests that the two biomarkers represent separate disease processes, and complement each other as diagnostic biomarkers."

A decrease in the levels of CSF Tf reflects the imbalance of brain's iron metabolism that is associated with sCJD. Being a part of the sCJD disease process, CSF Tf is likely to be a more precise indicator of sCJD than the current tests, Dr. Singh explains.

"CSF Tf is the first biomarker that is related to the underlying pathology in sCJD brains," Dr. Singh explains.

Presently, sCJD is diagnosed by testing for elevated levels of the proteins 14-3-3 and T-tau in the CSF of cases suspected of the disease. Since these biomarkers are elevated in several other diseases besides sCJD, the incidence of false positive results is high. Replacement of 14-3-3 with Tf increases the specificity of the test significantly, providing a superior biomarker combination for the diagnosis of sCJD.

The ability to accurately diagnose patients while they are still living is critical to prevent inadvertent spread of sCJD to healthy individuals, to reduce the misdiagnosis of potentially treatable causes of dementia, and to eventually develop potential therapies for sCJD, according to Dr. Singh.

As a part of their study, Dr. Singh and her team estimated levels of Tf in the CSF collected up to 24 months before death from confirmed cases of sCJD (n=99) and dementia of non-CJD origin (n=74). They found that levels of Tf were decreased significantly in sCJD cases compared to dementia of non-CJD origin. Further testing revealed that measurement of CSF Tf alone identified sCJD with a sensitivity of 85 percent, specificity of 72 percent, and accuracy of 80 percent. When combined with the surrogate biomarker T-tau, the CSF Tf and T-tau combination identified sCJD with an improved specificity of 87 percent and accuracy of 86 percent according to the research.

In addition to providing improved diagnostic accuracy, Dr. Singh notes that CSF Tf has several other advantages. It is resistant to degradation by enzymes, ensuring consistent results even in poorly preserved CSF samples; Tf-â2, the brain specific isoform of Tf is equally efficient in identifying sCJD and is likely to provide accurate results even from samples that are accidentally contaminated with blood during the collection process; and, Tf is abundant in the CSF relative to the currently used biomarkers 14-3-3 and T-tau, allowing accurate diagnosis from a small sample volume.

Moving forward, researchers will work to establish a user-friendly, quantitative test for CSF Tf to provide a quick and uniform method of diagnosis for sCJD. They will also continue testing CSF samples from sCJD and other forms of human and animal prion disorders to establish the earliest time point in the disease course when this test becomes positive.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.

Annually, the School of Medicine trains more than 800 M.D. and M.D./Ph.D. students and ranks in the top 20 among U.S. research-oriented medical schools as designated by U.S. News & World Report "Guide to Graduate Education."

The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.

Jessica Studeny | EurekAlert!
Further information:
http://www.case.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>