Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis

Neurobiol Aging. 2015 Feb;36(2):1072-4. doi: 10.1016/j.neurobiolaging.2014.10.019. Epub 2014 Oct 18.

Abstract

In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and total tau (t-tau) in CSF of ALS patients and control subjects. CSF p-tau and t-tau levels were measured in 60 consecutive ALS patients and 120 control subjects without neurodegenerative disease, using an established specific enzyme-linked immunosorbent assay method. Contrary to recent reports, CSF p-tau was not significantly reduced in ALS patients compared with control subjects (p = 0.287). However, CSF t-tau was significantly increased (p < 0.001). Correspondingly, the ratio of p-tau to t-tau was significantly reduced in ALS (p < 0.001). The area under the curve demonstrated poor sensitivity and specificity for p-tau, but moderate sensitivity and specificity for t-tau and p-tau/t-tau ratio. Thus, CSF p-tau by itself does not appear a suitable diagnostic biomarker for ALS, whereas CSF t-tau is a (probably unspecific) marker of the neuronal degeneration in ALS.

Keywords: Amyotrophic lateral sclerosis; Biomarker; Case-control study; Cerebrospinal fluid; Frontotemporal dementia; Phosphorylation; Tau.

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Disease Progression
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation
  • Sensitivity and Specificity
  • tau Proteins / cerebrospinal fluid*

Substances

  • Biomarkers
  • tau Proteins