Show simple item record

dc.contributor.authorVuono, Rominaen
dc.contributor.authorKouli, Antoninaen
dc.contributor.authorLegault, Emilie Men
dc.contributor.authorChagnon, Laurianeen
dc.contributor.authorAllinson, Kieren Sen
dc.contributor.authorLa Spada, Albertoen
dc.contributor.authorREGISTRY Investigators of the European Huntington's Disease Network,en
dc.contributor.authorBiunno, Idaen
dc.contributor.authorBarker, Rogeren
dc.contributor.authorDrouin-Ouellet, Janelleen
dc.date.accessioned2019-09-11T23:30:38Z
dc.date.available2019-09-11T23:30:38Z
dc.date.issued2020-03en
dc.identifier.issn0885-3185
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/296785
dc.description.abstractWhile Huntington’s disease (HD) is caused by a single dominant gene, it is clear that there are genetic modifiers that may influence the age of onset and disease progression. Objectives. Here, we sought to investigate whether new inflammation-related genetic variants may contribute to the onset and progression of HD. Methods. We first used post mortem brain material from patients at different stages of HD to look at the protein expression of TLR4 and TREM2. We then genotyped the TREM2 R47H gene variant and three TLR4 SNPs in a large cohort of HD patients from the European Huntington’s Disease Network REGISTRY. Results. We found an increase in the number of cells expressing TREM2 and TLR4 in post mortem brain samples from patients dying with HD. We also found that the TREM2 R47H gene variant was associated with changes in cognitive decline in the large cohort of HD patients, whereas two out of three TLR4 SNPs assessed were associated with changes in motor progression in this same group. Conclusions. These findings identify TREM2 and TLR4 as potential genetic modifiers for HD and suggest that inflammation influences disease progression in this condition.
dc.description.sponsorshipThe research leading to these results has received funding the European Research Council under the European Union’s Seventh Framework Programme: FP/2007-2013 NeuroStemcellRepair (no. 602278) to RAB and Fonds du Québec en Recherche, Santé (FRQS) to JDO. RV has received funding from Alzheimer's Research UK. AK has been supported by a PhD scholarship from the Onassis Foundation and a studentship by the Alborada Trust, and currently funded by a grant from the Evelyn Trust. RAB has received grants from NIHR; MRC; Wellcome Trust; Parkinson's UK; Huntington's Disease Association; Rosetrees Trust; Cure Parkinson's Trust, royalties from Wiley and Springer-Nature and consultancy monies from LCT; F-Prime; Fujifilm Cellular Dynamics International and Oxford Biomedica. RAB is an NIHR Senior Investigator. JDO is receiving salary support from FRQS and Parkinson Québec. The Cambridge Brain Bank is supported in part by NIHR.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherWiley-Blackwell
dc.rightsAll rights reserved
dc.subjectREGISTRY Investigators of the European Huntington's Disease Networken
dc.subjectBrainen
dc.subjectMyeloid Cellsen
dc.subjectHumansen
dc.subjectHuntington Diseaseen
dc.subjectAlzheimer Diseaseen
dc.subjectMembrane Glycoproteinsen
dc.subjectReceptors, Immunologicen
dc.subjectToll-Like Receptor 4en
dc.titleAssociation Between Toll-Like Receptor 4 (TLR4) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Genetic Variants and Clinical Progression of Huntington's Disease.en
dc.typeArticle
prism.endingPage408
prism.issueIdentifier3en
prism.publicationDate2020en
prism.publicationNameMovement disorders : official journal of the Movement Disorder Societyen
prism.startingPage401
prism.volume35en
dc.identifier.doi10.17863/CAM.43829
dcterms.dateAccepted2019-09-09en
rioxxterms.versionofrecord10.1002/mds.27911en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-03en
dc.contributor.orcidVuono, Romina [0000-0002-5162-3422]
dc.contributor.orcidKouli, Antonina [0000-0001-6553-6154]
dc.contributor.orcidBarker, Roger [0000-0001-8843-7730]
dc.contributor.orcidDrouin-Ouellet, Janelle [0000-0002-7645-0521]
dc.identifier.eissn1531-8257
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Commission FP7 Collaborative projects (CP) (unknown)
pubs.funder-project-idMRC (MC_PC_12009)
cam.orpheus.successThu Jan 30 10:39:15 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-11-14


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record