Researchers Identify Biomarker for Creutzfeldt-Jakob Disease

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.

What is Creutzfeldt-Jakob Disease?

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people per year worldwide; in the United States there are about 200 cases per year. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent of individuals die within 1 year. In the early stages of disease, people may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur.

There are three major categories of CJD:

* In sporadic CJD, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of CJD and accounts for at least 85 percent of cases.
* In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary.* In acquired CJD, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence that CJD is contagious through casual contact with a CJD patient. Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired CJD.