Utilidad clínica de la proteína tau total y la ratio con su fracción fosforilada en el diagnóstico de enfermedad de Creutzfeldt-Jakob

Abstract

Introduction: Creutzfeldt-Jakob disease (CJD) is the main human transmissible spongiform encephalopathy that presents with rapidly progressive dementia and fatal evolution. In the diagnostic strategy, surrogate biomarkers in cerebrospinal fluid (CSF) provide very useful initial information. The most widely used has been the 14-3-3 protein, but recently the total tau protein (T-tau) and its phosphorylated form (p-tau181) have gained interest, already used in the diagnosis of other neurodegenerative diseases. Material and methods: in this retrospective study we compare the diagnostic performance of the 14-3-3 protein (Western blot) with that of T-tau and p-tau181 proteins (electrochemiluminescence) in a cohort of 188 suspected CJD patients of which 18 were diagnosed (10 confirmed, 7 probable, one possible). Results: qualitative values (positive/negative) of the 14-3-3 protein were able to discriminate CJD from non-CJD patients, with low sensitivity (61%) and good specificity (98 %). In contrast, T-tau quantification (cut-off 800 pg/mL) and T-tau/ p-tau181 ratio (cut-off 28) improved CJD diagnosis, with high sensitivity (88 % and 94 %) and specificity (97 % and 98 %), respectively. Based on the above data, a CJD diagnostic algorithm based on T-tau, tau/p-tau181 and the confirmation test RT-QuIC (Real-Time Quaking-Induced Conversion) is proposed. Conclusions: CSF T-tau and p-tau181 proteins are first-line biomarkers with elevated diagnostic accuracy for CJD. Its automation in immunoassay platforms with improvements in analytical quality and response times increases its diagnostic utility.