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.
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