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altered prion protein expression pattern in csf as a biomarker for creutzfeldt-jakob disease朊蛋白表达模式的改变csf作为克雅二氏症的生物标志物
Altered Prion Protein Expression Pattern in CSF as a
Biomarker for Creutzfeldt-Jakob Disease
1,2 3 ´ 1,2,3 ´ 1,2 1,2
Mauricio Torres , Luis Cartier *, Jose Manuel Matamala , Nancy Hernandez , Ute Woehlbier ,
Claudio Hetz1,2,4,5*
1 Neuroscience Biomedical Institute, Faculty of Medicine, University of Chile, Santiago, Chile, 2 Center for Molecular Studies of the Cell, Institute of Biomedical Sciences,
University of Chile, Santiago, Chile, 3 Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile, 4 Neurounion Biomedical Foundation,
Santiago, Chile, 5 Harvard School of Public Health, Boston, Massachusetts, United States of America
Abstract
Creutzfeldt-Jakob disease (CJD) is the most frequent human Prion-related disorder (PrD). The detection of 14-3-3 protein in
the cerebrospinal fluid (CSF) is used as a molecular diagnostic criterion for patients clinically compatible with CJD. However,
there is a pressing need for the identification of new reliable disease biomarkers. The pathological mechanisms leading to
accumulation of 14-3-3 protein in CSF are not fully understood, however neuronal loss followed by cell lysis is assumed to
cause the increase in 14-3-3 levels, which also occurs in conditions such as brain ischemia. Here we investigated the relation
between the levels of 14-3-3 protein, Lactate dehydrogenase (LDH) activity and expression of the prion protein (PrP) in CSF
of sporadic and familial CJD cases. Unexpectedly, we found normal levels of LDH activity in CJD cases with moderate levels
of 14-3-3 protein. Increased LDH activity was only observed in a percentage of the CSF samples that also exhibit
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