Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: An elusive quest

Research output: Contribution to journalArticle


Background Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer's disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD. Methods 86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau (181)). Patients with FTD were grouped based on their Aβ 42 level into those likely to have underlying Alzheimer's disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology. Results Significantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau (181) /T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109. Conclusions Despite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.


  • Martha S. Foiani
  • Claudia Cicognola
  • Natalia Ermann
  • Ione O.C. Woollacott
  • Carolin Heller
  • Amanda J. Heslegrave
  • Ashvini Keshavan
  • Ross W. Paterson
  • Keqiang Ye
  • Johannes Kornhuber
  • Nick C. Fox
  • Jonathan M. Schott
  • Jason D. Warren
  • Piotr Lewczuk
  • Henrik Zetterberg
  • Kaj Blennow
  • Kina Höglund
  • Jonathan D. Rohrer
External organisations
  • University College London
  • Sahlgrenska Academy
  • University Hospital Erlangen
  • Emory University
  • Medical University of Bialystok
  • UK Dementia Research Institute
  • Sahlgrenska University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • CSF, frontotemporal dementia, tau
Original languageEnglish
Pages (from-to)740-746
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number7
Publication statusPublished - 2019 Jul 1
Publication categoryResearch
Externally publishedYes