Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer's Disease

CSF total-tau (t-tau) became a standard cerebrospinal fluid biomarker in Alzheimer's disease (AD). In parallel, extremely elevated levels were observed in Creutzfeldt-Jakob disease (CJD). Therefore, tau is also considered as an alternative CJD biomarker, potentially complicating the interpretat...

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Veröffentlicht in:Viruses 2022-01, Vol.14 (2), p.276
Hauptverfasser: Hermann, Peter, Haller, Philip, Goebel, Stefan, Bunck, Timothy, Schmidt, Christian, Wiltfang, Jens, Zerr, Inga
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Sprache:eng
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Zusammenfassung:CSF total-tau (t-tau) became a standard cerebrospinal fluid biomarker in Alzheimer's disease (AD). In parallel, extremely elevated levels were observed in Creutzfeldt-Jakob disease (CJD). Therefore, tau is also considered as an alternative CJD biomarker, potentially complicating the interpretation of results. We investigated CSF t-tau and the t-tau/phosphorylated tau181 ratio in the differential diagnosis of sCJD and rapidly-progressive AD (rpAD). In addition, high t-tau concentrations and associated tau-ratios were explored in an unselected laboratory cohort. Retrospective analyses included = 310 patients with CJD ( = 205), non-rpAD ( = 65), and rpAD ( = 40). The diagnostic accuracies of biomarkers were calculated and compared. Differential diagnoses were evaluated in patients from a neurochemistry laboratory with CSF t-tau >1250 pg/mL ( = 199 out of 7036). CSF t-tau showed an AUC of 0.942 in the discrimination of sCJD from AD and 0.918 in the discrimination from rpAD. The tau ratio showed significantly higher AUCs ( < 0.001) of 0.992 versus non-rpAD and 0.990 versus rpAD. In the neurochemistry cohort, prion diseases accounted for only 25% of very high CSF t-tau values. High tau-ratios were observed in CJD, but also in non-neurodegenerative diseases. CSF t-tau is a reliable biomarker for sCJD, but false positive results may occur, especially in rpAD and acute encephalopathies. The t-tau/p-tau ratio may improve the diagnostic accuracy in centers where specific biomarkers are not available.
ISSN:1999-4915
1999-4915
DOI:10.3390/v14020276