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

Viruses. 2022 Jan 28;14(2):276. doi: 10.3390/v14020276.

Abstract

Background: 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.

Methods: Retrospective analyses included n = 310 patients with CJD (n = 205), non-rpAD (n = 65), and rpAD (n = 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 (n = 199 out of 7036).

Results: 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 (p < 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.

Conclusions: 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.

Keywords: Alzheimer’s disease; Creutzfeldt-Jakob disease; biomarker; cerebrospinal fluid; rapidly-progressive dementia; tau; tau-ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / cerebrospinal fluid
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Biomarkers / cerebrospinal fluid
  • Brain Diseases / cerebrospinal fluid
  • Brain Diseases / diagnosis
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Diagnosis, Differential
  • False Positive Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid*

Substances

  • 14-3-3 Proteins
  • Biomarkers
  • MAPT protein, human
  • tau Proteins

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic