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Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: An elusive quest
- Article/chapterEnglish2019
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LIBRIS-ID:oai:gup.ub.gu.se/281620
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https://gup.ub.gu.se/publication/281620URI
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https://doi.org/10.1136/jnnp-2018-319266DOI
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Subject category:art swepub-publicationtype
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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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Cicognola, ClaudiaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xciccl
(author)
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Ermann, N.
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Woollacott, I. O. C.
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Heller, C.
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Heslegrave, A. J.
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Keshavan, A.
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Paterson, R. W.
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Ye, K.
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Kornhuber, J.
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Fox, N. C.
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Schott, J. M.
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Warren, J. D.
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Lewczuk, P.
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
(author)
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Höglund, Kina,1976Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xgukri
(author)
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Rohrer, J. D.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Journal of Neurology, Neurosurgery and Psychiatry: BMJ90:7, s. 740-7460022-30501468-330X
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Foiani, M. S.
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Cicognola, Claud ...
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Ermann, N.
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Woollacott, I. O ...
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Heller, C.
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Heslegrave, A. J ...
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Keshavan, A.
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Paterson, R. W.
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Ye, K.
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Kornhuber, J.
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Fox, N. C.
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Schott, J. M.
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Warren, J. D.
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Lewczuk, P.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Höglund, Kina, 1 ...
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Rohrer, J. D.
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University of Gothenburg