RT Journal Article
SR Electronic
T1 Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 740
OP 746
DO 10.1136/jnnp-2018-319266
VO 90
IS 7
A1 Martha S Foiani
A1 Claudia Cicognola
A1 Natalia Ermann
A1 Ione O C Woollacott
A1 Carolin Heller
A1 Amanda J Heslegrave
A1 Ashvini Keshavan
A1 Ross W Paterson
A1 Keqiang Ye
A1 Johannes Kornhuber
A1 Nick C Fox
A1 Jonathan M Schott
A1 Jason D Warren
A1 Piotr Lewczuk
A1 Henrik Zetterberg
A1 Kaj Blennow
A1 Kina Höglund
A1 Jonathan D Rohrer
YR 2019
UL http://jnnp.bmj.com/content/90/7/740.abstract
AB 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 Aβ42 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.