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New biomarker for fatal brain disease identified

Scientists 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.

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Scientists 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 research team included Neena Singh and colleagues at Case Western Reserve University School of Medicine.

The finding 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, Singh's team found that levels of the iron-transport protein transferring (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.

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, 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.

As a part of their study, Singh and her team estimated levels of Tf in the CSF collected up to 24 months before death from confirmed cases of sCJD and dementia of non-CJD origin.

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.

The study was published in the March 9th issue of PLoS ONE.

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