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dc.contributor.authorHolland, Negin
dc.contributor.authorJones, Simon
dc.contributor.authorSavulich, George
dc.contributor.authorWiggins, Julie K
dc.contributor.authorHong, Young
dc.contributor.authorFryer, Timothy
dc.contributor.authorManavaki, Roido
dc.contributor.authorSephton, Selena Milicevic
dc.contributor.authorBoros, Istvan
dc.contributor.authorMalpetti, Maura
dc.contributor.authorHezemans, Frank
dc.contributor.authorAigbirhio, Franklin
dc.contributor.authorColes, Jonathan
dc.contributor.authorO'Brien, John
dc.contributor.authorRowe, James
dc.date.accessioned2020-06-11T23:30:27Z
dc.date.available2020-06-11T23:30:27Z
dc.date.issued2020-10
dc.identifier.issn0885-3185
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/306715
dc.description.abstractBACKGROUND: Synaptic loss is a prominent and early feature of many neurodegenerative diseases. OBJECTIVES: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS). METHODS: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment. RESULTS: Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson's syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke's Cognitive Examination (R = 0.52; P = 0.01). CONCLUSIONS: We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherWiley
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectSupranuclear Palsy, Progressive
dc.subjectAlzheimer Disease
dc.subjectTauopathies
dc.subjectAtrophy
dc.subjectPositron-Emission Tomography
dc.titleSynaptic Loss in Primary Tauopathies Revealed by [11 C]UCB-J Positron Emission Tomography.
dc.typeArticle
prism.endingPage1842
prism.issueIdentifier10
prism.publicationDate2020
prism.publicationNameMov Disord
prism.startingPage1834
prism.volume35
dc.identifier.doi10.17863/CAM.53803
dcterms.dateAccepted2020-06-08
rioxxterms.versionofrecord10.1002/mds.28188
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-10
dc.contributor.orcidHolland, Negin [0000-0003-3813-0882]
dc.contributor.orcidJones, Simon [0000-0001-9695-0702]
dc.contributor.orcidManavaki, Roido [0000-0002-4384-6626]
dc.contributor.orcidSephton, Selena Milicevic [0000-0002-1105-6726]
dc.contributor.orcidMalpetti, Maura [0000-0001-8923-9656]
dc.contributor.orcidHezemans, Frank [0000-0003-0092-3289]
dc.contributor.orcidAigbirhio, Franklin [0000-0001-9453-5257]
dc.contributor.orcidColes, Jonathan [0000-0003-4013-679X]
dc.contributor.orcidO'Brien, John [0000-0002-0837-5080]
dc.contributor.orcidRowe, James [0000-0001-7216-8679]
dc.identifier.eissn1531-8257
rioxxterms.typeJournal Article/Review
pubs.funder-project-idPatrick Berthoud Charitable Trust (via Charities Aid Foundation) (Unknown)
pubs.funder-project-idWellcome Trust (103838/Z/14/Z)
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idMedical Research Council (MR/M024873/1)
pubs.funder-project-idMedical Research Council (MC_U105597119)
pubs.funder-project-idMedical Research Council (MR/M009041/1)
pubs.funder-project-idMedical Research Council (MC_UU_00005/12)
cam.issuedOnline2020-07-11
cam.orpheus.successMon Jul 13 08:27:02 BST 2020 - Embargo updated
cam.orpheus.counter5
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International (CC BY)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY)