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

Artikel i vetenskaplig tidskrift
Författare M. S. Foiani
Claudia Cicognola
N. Ermann
I. O. C. Woollacott
C. Heller
A. J. Heslegrave
A. Keshavan
R. W. Paterson
K. Ye
J. Kornhuber
N. C. Fox
J. M. Schott
J. D. Warren
P. Lewczuk
Henrik Zetterberg
Kaj Blennow
Kina Höglund
J. D. Rohrer
Publicerad i Journal of Neurology, Neurosurgery and Psychiatry
Volym 90
Sidor 740-746
ISSN 0022-3050
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 740-746
Språk en
Länkar dx.doi.org/10.1136/jnnp-2018-319266
Ämnesord CSF, frontotemporal dementia, tau
Ämneskategorier Neurovetenskaper

Sammanfattning

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. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

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