title: Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Deuschle
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: Tim W
authors.initials: TW
authors.lastname: Rattay
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany. Electronic address: matthis.synofzik@uni-tuebingen.de.
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D016875:tau Proteins
keywords: Amyotrophic lateral sclerosis; Biomarker; Case-control study; Cerebrospinal fluid; Frontotemporal dementia; Phosphorylation; Tau