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dc.contributor.authorBevan-Jones, William Richarden
dc.contributor.authorCope, Thomas Edmunden
dc.contributor.authorJones, PSen
dc.contributor.authorPassamonti, Lucaen
dc.contributor.authorHong, Young Teaen
dc.contributor.authorFryer, Timothy Daviden
dc.contributor.authorArnold, Ren
dc.contributor.authorAllinson, Ken
dc.contributor.authorColes, Jonathan Peteren
dc.contributor.authorAigbirhio, Franklin Imoen
dc.contributor.authorPatterson, Ken
dc.contributor.authorO'Brien, John Tiernanen
dc.contributor.authorRowe, James Benedicten
dc.date.accessioned2017-08-10T09:16:35Z
dc.date.available2017-08-10T09:16:35Z
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266170
dc.description.abstractINTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [18F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with ‘right’ semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [18F]AV-1451. Two independent preprocessing methods were used. For both methods, all patients had clearly elevated binding potential (BPND (non-displaceable binding potential)) in temporal lobes, lateralising according to their clinical syndrome and evident in raw images. Region of interest analyses confirmed that BPND was significantly increased in temporal regions, insula and fusiform gyrus, consistent with those areas known to be most affected in semantic dementia. Hierarchical cluster analysis, based on the distribution of [18F]AV-1451 binding potential, separated semantic dementia from controls with 86% sensitivity and 100% specificity. CONCLUSIONS:[18F]AV-1451 binds in vivo regions that are likely to contain TDP-43 and not significant tau pathology. While this suggests a non-tau target for [18F]AV-1451, the pathological regions in semantic dementia do not normally contain significant levels of recently proposed ‘off target’ binding sites for [18F]AV-1451, such as neuronal monoamine oxidase or neuromelanin. Postmortem and longitudinal data will be useful to assess the utility of [18F]AV-1451 to differentiate and track different types of frontotemporal lobar degeneration.
dc.description.sponsorshipThis work was supported by the National Institute for Health Research Biomedical Research Centre and Biomedical Research Unit in Dementia; the Wellcome Trust (JBR 103838); the Association of British Neurologists and the Patrick Berthoud Charitable Trust (TEC).
dc.language.isoenen
dc.publisherBMJ
dc.relation.isreplacedby1810/273221
dc.relation.isreplacedbyhttps://www.repository.cam.ac.uk/handle/1810/273221
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.title[18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasiaen
dc.typeArticle
prism.publicationNameJournal of Neurology, Neurosurgery and Psychiatryen
dc.identifier.doi10.17863/CAM.12506
dc.identifier.doi10.17863/CAM.12506
dcterms.dateAccepted2017-07-27en
rioxxterms.versionofrecord10.1136/jnnp-2017-316402en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-07-27en
dc.contributor.orcidColes, Jonathan Peter [0000-0003-4013-679X]
dc.contributor.orcidO'Brien, John Tiernan [0000-0002-0837-5080]
dc.contributor.orcidRowe, James Benedict [0000-0001-7216-8679]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (103838/Z/14/Z)
pubs.funder-project-idAssociation of British Neurologists (ABN) (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
cam.issuedOnline2017-09-14en
cam.orpheus.successThu Jan 30 12:59:28 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
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