Searching for Reliable Premortem Protein Biomarkers for Prion Diseases

Progress and Challenges to Date

Di Ma; Lingjun Li


Expert Rev Proteomics. 2012;9(3):267-280. 

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Expert Commentary

Given the infectious and incurable nature of prion diseases, early diagnosis is highly desirable. Although current antibody-based assays allow specific and sensitive detection of biomarker PrPSc in brain tissue, they cannot be applied to premortem screening in readily accessible biological fluids due to the low concentration of misfolded PrPSc. MS-based proteomics has emerged as a powerful tool to identify surrogate protein biomarkers that are associated with prion diseases in complex biological samples such as plasma/serum, CSF and urine. In combination with prefractionation and affinity enrichment strategies, quantitative MS analysis allows more low-abundance proteins to be detected.

While the list of potential biomarkers for prion disease is growing, the validatory studies on these proteins are not being carried out at the same pace. Reasons for this include the inherent problems of prion diseases such as the small number of clinical cases and the long incubation period. Also, ELISA-based verification is limited by the availability of the antibodies and is not suitable for multiplexed assays. Therefore, the development of verification platform based on MRM-MS seems to be a promising alternative. As some of the pathways in neuropathogenesis of prion diseases also exist in other neurodegenerative as well as other infectious diseases, the specificity of individual potential biomarkers needs to be examined carefully in the verification phase. It would be prudent to use a combination of multiple biomarkers rather than one single biomarker in order to reach higher sensitivity and specificity.


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