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Research identifies biomarker for sporadic Creutzfeldt-Jakob disease

Singh A. PLoS One. 2011;doi:10.1371/journal.pone.0016804.

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Levels of the iron-transport protein transferrin are significantly decreased in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease well before the end stage of the disease, according to a study published online.

This discovery may potentially allow earlier diagnosis, according to Neena Singh, MD, PhD, of Case Western Reserve University School of Medicine, Cleveland.

Singh and colleagues said transferrin levels are decreased enough to “distinguish sporadic Creutzfeldt-Jakob disease (sCJD) from dementia of non-CJD origin” in the earlier stages of the disease. Also, using the biomarker T-tau combined with transferrin increases diagnostic accuracy even further.

A decrease in cerebrospinal fluid (CSF) levels of transferrin reflects the imbalance of the brain’s iron metabolism that is associated with sCJD. Being a part of the sCJD process, CSF levels of transferrin are likely to be a more precise indicator of sCJD than the current tests, Singh and colleagues said.

As a part of their study, Singh and colleagues estimated levels of transferrin in the CSF that were collected up to 24 months before death from confirmed cases of sCJD (n=99) and dementia of non-CJD origin (n=74).

The researchers found that levels of transferrin were decreased significantly in patients with sCJD compared with dementia of non-CJD origin. Further testing revealed that measurement of CSF levels of transferrin alone identified sCJD with a sensitivity of 85%, specificity of 72% and accuracy of 80%. When combined with the surrogate biomarker T-tau, the CSF levels of transferrin and T-tau combination identified sCJD with an improved specificity of 87% and accuracy of 86%, according to the researchers.

Moving forward, the researchers said they plan to establish a user-friendly, quantitative test for CSF levels of transferrin 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.

Disclosure: This study was supported by funds from an NIH grant.

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