Phosphorylated tau 181 (p-tau181) as an innovative, fast and robust biomarker for cerebrospinal fluid leaks

J Neurol. 2024 Oct;271(10):6724-6728. doi: 10.1007/s00415-024-12624-6. Epub 2024 Aug 20.

Abstract

Background: Cerebrospinal fluid (CSF) leaks can lead to serious complications if left untreated, making rapid and accurate diagnosis essential. Biomarkers such as β2-transferrin (B2TRF) and β-trace protein are used to detect CSF leaks, but their limitations warrant the exploration of alternative markers. This study investigates the potential of phosphorylated tau at threonine 181 (p-tau181) as a biomarker for CSF leaks.

Methods: Samples from 56 subjects were analyzed for B2TRF and p-tau181 using immunoaffinity blotting and chemiluminescent enzyme immunoassay, respectively. Data analysis included Mann-Whitney test to assess the overall difference in median p-tau181 concentrations between B2TRF positive and negative patients and a receiver operating characteristic (ROC) curve analysis to determine optimal p-tau181 cutoff values for predicting B2TRF positivity.

Results: p-tau181 levels were significantly higher in B2TRF positive samples compared to negative samples (p < 0.001). ROC analysis showed high diagnostic performance for p-tau181, with an optimal cutoff of 13.22 pg/mL providing 92.0% sensitivity and 93.1% specificity. Excluding hemolyzed samples improved further the diagnostic performances, maintaining high sensitivity (90.9%) and achieving perfect specificity (100.0%).

Conclusions: This study highlights the potential of p-tau181 as a valuable biomarker for the detection of CSF leaks due to its high diagnostic accuracy and practical advantages over the current biomarkers. The characteristics of p-tau181 assay being both quantitative and rapid, with high diagnostic accuracy, suggest that it could be a valuable tool for the detection of CSF leaks. Further research are now needed to validate these findings.

Keywords: Biomarker; Cerebrospinal; Leak; Neurology; p-tau181.

MeSH terms

  • Adult
  • Aged
  • Biomarkers* / cerebrospinal fluid
  • Cerebrospinal Fluid Leak* / cerebrospinal fluid
  • Cerebrospinal Fluid Leak* / diagnosis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation
  • ROC Curve
  • Sensitivity and Specificity
  • Transferrin / analysis
  • Transferrin / cerebrospinal fluid
  • tau Proteins* / cerebrospinal fluid

Substances

  • tau Proteins
  • Biomarkers
  • MAPT protein, human
  • Transferrin