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CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

2022-11Journal article Open access
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dc.contributor.authorthe Genetic FTD Initiative, GENFI
dc.contributor.authorWoollacott, Ione O.C.
dc.contributor.authorSwift, Imogen J.
dc.contributor.authorSogorb-Esteve, Aitana
dc.contributor.authorHeller, Carolin
dc.contributor.authorKnowles, Kathryn
dc.contributor.authorBouzigues, Arabella
dc.contributor.authorRussell, Lucy L.
dc.contributor.authorPeakman, Georgia
dc.contributor.authorGreaves, Caroline V.
dc.contributor.authorConvery, Rhian
dc.contributor.authorHeslegrave, Amanda
dc.contributor.authorRowe, James B.
dc.contributor.authorBorroni, Barbara
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorTiraboschi, Pietro
dc.contributor.authorMasellis, Mario
dc.contributor.authorTartaglia, Maria Carmela
dc.contributor.authorFinger, Elizabeth
dc.contributor.authorvan Swieten, John C.
dc.contributor.authorSeelaar, Harro
dc.contributor.authorJiskoot, Lize
dc.contributor.authorSorbi, Sandro
dc.contributor.authorButler, Chris R.
dc.contributor.authorGraff, Caroline
dc.contributor.authorGerhard, Alexander
dc.contributor.authorLaforce, Robert
dc.contributor.authorSanchez-Valle, Raquel
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorMoreno, Fermin
dc.contributor.authorSynofzik, Matthis
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorDucharme, Simon
dc.contributor.authorBer, Isabelle Le
dc.contributor.authorLevin, Johannes
dc.contributor.authorOtto, Markus
dc.contributor.authorPasquier, Florence
dc.contributor.authorSantana, Isabel
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorRohrer, Jonathan D.
dc.contributor.authorNelson, Annabel
dc.contributor.authorBocchetta, Martina
dc.contributor.authorCash, David
dc.contributor.authorThomas, David L.
dc.contributor.authorTodd, Emily
dc.contributor.authorBenotmane, Hanya
dc.contributor.authorNicholas, Jennifer
dc.contributor.authorSamra, Kiran
dc.contributor.authorMaruta, Carolina
dc.contributor.authordo Couto, Frederico Simões
dc.contributor.authorAlmeida, Maria Rosário
dc.date.accessioned2023-04-26T08:50:18Z
dc.date.available2023-04-26T08:50:18Z
dc.date.issued2022-11
dc.description.abstractBackground: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. Methods: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. Results: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. Conclusions: Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1002/acn3.51672pt_PT
dc.identifier.eid85139878909
dc.identifier.issn2328-9503
dc.identifier.pmcPMC9639635
dc.identifier.pmid36245297
dc.identifier.urihttp://hdl.handle.net/10400.14/40953
dc.identifier.wos000868509300001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleCSF glial markers are elevated in a subset of patients with genetic frontotemporal dementiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1777pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1764pt_PT
oaire.citation.titleAnnals of Clinical and Translational Neurologypt_PT
oaire.citation.volume9pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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