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dc.contributor.authorChouliaras, Leonidas
dc.contributor.authorThomas, Alan
dc.contributor.authorMalpetti, Maura
dc.contributor.authorDonaghy, Paul
dc.contributor.authorKane, Joseph
dc.contributor.authorMak, Elijah
dc.contributor.authorSavulich, George
dc.contributor.authorPrats-Sedano, Maria A
dc.contributor.authorHeslegrave, Amanda J
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorSu, Li
dc.contributor.authorRowe, James Benedict
dc.contributor.authorO'Brien, John Tiernan
dc.date.accessioned2022-01-31T10:13:10Z
dc.date.available2022-01-31T10:13:10Z
dc.date.issued2022-06
dc.date.submitted2021-08-10
dc.identifier.citationJournal of Neurology, Neurosurgery, and Psychiatry, page jnnp-2021-327788
dc.identifier.issn0022-3050
dc.identifier.otherjnnp-2021-327788
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333461
dc.description.abstractOBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
dc.description.sponsorshipb. Funding This study was funded by the Cambridge Centre for Parkinson-Plus, the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge and the NIHR Newcastle Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The UK Dementia Research Institute, receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the UK Dementia Research Institute at UCL, the Wellcome Trust and an anonymous donor.
dc.languageen
dc.publisherBMJ
dc.subjectNeurodegeneration
dc.subject1506
dc.subjectalzheimer's disease
dc.subjectlewy body dementia
dc.subjectfrontotemporal dementia
dc.subjectdementia
dc.subjectmovement disorders
dc.titleDifferential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy.
dc.typeArticle
dc.date.updated2022-01-31T10:13:10Z
prism.publicationNameJ Neurol Neurosurg Psychiatry
dc.identifier.doi10.17863/CAM.80885
dcterms.dateAccepted2021-12-01
rioxxterms.versionofrecord10.1136/jnnp-2021-327788
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2022-01-25
dc.contributor.orcidChouliaras, Leonidas [0000-0002-3052-3879]
dc.contributor.orcidMalpetti, Maura [0000-0001-8923-9656]
dc.contributor.orcidZetterberg, Henrik [0000-0003-3930-4354]
dc.contributor.orcidRowe, James Benedict [0000-0001-7216-8679]
dc.identifier.eissn1468-330X
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idWellcome Trust (220258/Z/20/Z)
pubs.funder-project-idMedical Research Council (MR/M009041/1)
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2022-01-25
rioxxterms.freetoread.startdate2022-01-25
rioxxterms.freetoread.startdate2022-01-25


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