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Biomarker May Lead to Diagnostic Test for Creutzfeldt-Jakob Disease


Creutzfeldt-Jakob disease is a rare form of brain damage that leads to a rapid decrease of mental function. There is no cure and accurate diagnosis can only be obtained by brain biopsy or autopsy. Researchers at Case Western Reserve University School of Medicine believe they have identified the first disease-specific biomarker that may eventually provide a basis for a definitive diagnostic test for the disease while patients are still alive.

Creutzfeldt-Jakob Disease (CJD) occurs in about one out of every 1 million people. It usually first appears between ages 20 and 70, with average age of onset of symptoms in the late 50’s. CJD can be grouped into two forms of classic disease – sporadic and familial. Sporadic CJD (sCJD) makes up the majority of cases.

CJD is thought to result from a prion disorder. A prion is a protein that causes normal proteins to fold abnormally, affecting their ability to function. Spinal taps are currently used to test for elevated levels of the proteins 14-3-3 and T-tau in patients suspected of having the disease, but because these markers are elevated in several other diseases as well, the incidence of false positives is high.

Neena Singh MD PhD, an associate professor of pathology, and colleagues found that levels of the iron transport protein transferring (Tf) are significantly decreased in the cerebrospinal fluid of patients with sCJD well before the end stage of the disease. This decrease reflects an imbalance in the brain’s iron metabolism.

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“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.”

Tf is abundant in CSF relative to the currently used biomarkers, allowing accurate diagnosis from a small sample volume. In addition to providing improved diagnostic accuracy, Dr. Singh notes that CSF Tf is also resistant to degradation by enzymes, ensuring consistent results even in poorly preserved CSF samples.

The ability to accurately diagnose patients while they are still living is critical to reducing the misdiagnosis of potential treatable causes of dementia and to eventually developing potential therapies for sCJD.

Dr. Singh intends to continue the research 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 prion disorders to establish the earliest time point in the disease course when the test becomes positive.

Journal Reference:
Singh A, Beveridge ′J, Singh N, 2011 Decreased CSF Transferrin in sCJD: A Potential Pre-Mortem Diagnostic Test for Prion Disorders. PLoS ONE 6(3): e16804. doi:10.1371/journal.pone.0016804