{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:05:56Z","timestamp":1777395956386,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,10,26]]},"abstract":"<jats:p>Background: In Alzheimer\u2019s disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD. Objective: We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition. Methods: Two cohorts, each including 29 participants (healthy controls [HC], prodromal AD, and AD dementia patients), underwent 18F-THK5317 or 18F-flortaucipir PET, T1-weighted MRI, and neuropsychological assessment. For each subject, we quantified regional 18F-THK5317 and 18F-flortaucipir uptake within six bilateral and two composite regions of interest. We assessed global brain atrophy for each individual by quantifying the brain volume index, a measure of brain volume-to-cerebrospinal fluid ratio. We then quantified the discriminative ability of regional 18F-THK5317, 18F-flortaucipir, and brain volume index between diagnostic groups, and their associations with cognition in patients. Results: Both 18F-THK5317 and 18F-flortaucipir outperformed global brain atrophy in discriminating between HC and both prodromal AD and AD dementia groups. 18F-THK5317 provided the highest discriminative ability between HC and prodromal AD groups. 18F-flortaucipir performed best at discriminating between prodromal and dementia stages of AD. Across all patients, both tau tracers were predictive of RAVL learning, but only 18F-flortaucipir predicted MMSE. Conclusion: Our results warrant further in vivo head-to-head and antemortem-postmortem evaluations. These validation studies are needed to select tracers with high clinical validity as biomarkers for early diagnosis, prognosis, and disease staging, which will facilitate their incorporation in clinical practice and therapeutic trials.<\/jats:p>","DOI":"10.3233\/jad-210614","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T13:18:12Z","timestamp":1631279892000},"page":"103-117","source":"Crossref","is-referenced-by-count":6,"title":["Assessment of Tau Pathology as Measured by 18F-THK5317 and 18F-Flortaucipir PET and Their Relation to Brain Atrophy and Cognition in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"84","author":[{"given":"Elisa","family":"Colato","sequence":"first","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Chiotis","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Neurology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam S.","family":"Mazrina","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laetitia","family":"Lemoine","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaleena","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agneta","family":"Nordberg","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"},{"name":"Theme Aging, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-8141","authenticated-orcid":false,"given":"Elena","family":"Rodriguez-Vieitez","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-210614_ref1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-210614_ref2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"key":"10.3233\/JAD-210614_ref3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1001\/archneur.1995.00540250089017","article-title":"Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer\u2019s disease","volume":"52","author":"Bierer","year":"1995","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-210614_ref4","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1212\/01.WNL.0000063311.58879.01","article-title":"Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer\u2019s disease","volume":"60","author":"Giannakopoulos","year":"2003","journal-title":"Neurology"},{"key":"10.3233\/JAD-210614_ref5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer disease neuropathologic changes with cognitive status: A review of the literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-210614_ref6","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41380-018-0342-8","article-title":"Tau PET imaging in neurodegenerative tauopathies-still a challenge","volume":"24","author":"Leuzy","year":"2019","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-210614_ref7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.arr.2015.12.010","article-title":"Advances in the development of tau PET radiotracers and their clinical applications","volume":"30","author":"Okamura","year":"2016","journal-title":"Ageing Res Rev"},{"key":"10.3233\/JAD-210614_ref8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nrneurol.2014.257","article-title":"Dementia in 2014. Towards early diagnosis in Alzheimer disease","volume":"11","author":"Nordberg","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-210614_ref9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1053\/j.semnuclmed.2020.12.004","article-title":"Imaging of tau pathology in neurodegenerative diseases: An update","volume":"51","author":"Beyer","year":"2020","journal-title":"Semin Nucl Med"},{"key":"10.3233\/JAD-210614_ref10","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.2967\/jnumed.112.117341","article-title":"Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease","volume":"54","author":"Okamura","year":"2013","journal-title":"J Nucl Med"},{"key":"10.3233\/JAD-210614_ref11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3233\/JAD-122059","article-title":"Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807","volume":"34","author":"Chien","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-210614_ref12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40478-015-0220-4","article-title":"Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue","volume":"3","author":"Lemoine","year":"2015","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-210614_ref13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40478-016-0315-6","article-title":"An autoradiographic evaluation of AV-1451 Tau PET in dementia","volume":"4","author":"Lowe","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-210614_ref14","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00401-017-1740-8","article-title":"[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging","volume":"134","author":"Marqui\u00e9","year":"2017","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-210614_ref15","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/ana.24517","article-title":"Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue","volume":"78","author":"Marqui\u00e9","year":"2015","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-210614_ref16","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1001\/jamaneurol.2020.0528","article-title":"Positron emission tomography imaging with [18F]flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes","volume":"77","author":"Fleisher","year":"2020","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-210614_ref17","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jalz.2019.09.079","article-title":"Tau-positron emission tomography correlates with neuropathology findings","volume":"16","author":"Lowe","year":"2020","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-210614_ref18","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13195-017-0325-z","article-title":"Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains","volume":"9","author":"Lemoine","year":"2017","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-210614_ref19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-017-0162-3","article-title":"Tau PET imaging: Present and future directions","volume":"12","author":"Saint-Aubert","year":"2017","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-210614_ref20","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12321"},{"key":"10.3233\/JAD-210614_ref21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s13139-020-00657-4","article-title":"Tau imaging: New era of neuroimaging for Alzheimer\u2019s disease","volume":"54","author":"Kim","year":"2020","journal-title":"Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-210614_ref22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-210614_ref23","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1093\/brain\/awaa088","article-title":"Microglial activation and tau burden predict cognitive decline in Alzheimer\u2019s disease","volume":"143","author":"Malpetti","year":"2020","journal-title":"Brain"},{"key":"10.3233\/JAD-210614_ref24","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1007\/s00259-016-3363-z","article-title":"Imaging in-vivo tau pathology in Alzheimer\u2019s disease with THK5317 PET in a multimodal paradigm","volume":"43","author":"Chiotis","year":"2016","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-210614_ref25","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s00259-012-2237-2","article-title":"A European multicentre PET study of fibrillar amyloid in Alzheimer\u2019s disease","volume":"40","author":"Nordberg","year":"2013","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-210614_ref26","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2019s Disease","volume":"34","author":"McKhann","year":"1984","journal-title":"Neurology"},{"key":"10.3233\/JAD-210614_ref28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1001\/archneur.56.3.303","article-title":"Mild cognitive impairment: Clinical characterization and outcome","volume":"56","author":"Petersen","year":"1999","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-210614_ref29","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0815-4"},{"key":"10.3233\/JAD-210614_ref30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13195-016-0204-z","article-title":"Regional tau deposition measured by [18F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer\u2019s disease","volume":"8","author":"Saint-Aubert","year":"2016","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-210614_ref31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/hbm.10123","article-title":"Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe","volume":"19","author":"Hammers","year":"2003","journal-title":"Hum Brain Mapp"},{"key":"10.3233\/JAD-210614_ref32","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.dadm.2018.01.007","article-title":"Tau positron emission tomography imaging in tauopathies: The added hurdle of off-target binding","volume":"10","author":"Lemoine","year":"2018","journal-title":"Alzheimers Dement (Amst)"},{"key":"10.3233\/JAD-210614_ref33","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00259-019-04305-8","article-title":"Cross-interaction of tau PET tracers with monoamine oxidase B: Evidence from in silico modelling and in vivo imaging","volume":"46","author":"Murugan","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-210614_ref34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000442443","article-title":"Measuring global brain atrophy with the brain volume\/cerebrospinal fluid index: Normative values, cut-offs and clinical associations","volume":"16","author":"Orellana","year":"2016","journal-title":"Neurodegener Dis"},{"key":"10.3233\/JAD-210614_ref35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13195-019-0518-8","article-title":"Tau and atrophy: Domain-specific relationships with cognition","volume":"11","author":"Digma","year":"2019","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-210614_ref36","doi-asserted-by":"crossref","first-page":"e601","DOI":"10.1212\/WNL.0000000000006875","article-title":"Associations between tau, A\u03b2, and cortical thickness with cognition in Alzheimer disease","volume":"92","author":"Ossenkoppele","year":"2019","journal-title":"Neurology"},{"key":"10.3233\/JAD-210614_ref37","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.neuroimage.2017.05.058","article-title":"Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer\u2019s disease","volume":"157","author":"Maass","year":"2017","journal-title":"NeuroImage"},{"key":"10.3233\/JAD-210614_ref38","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer\u2019s disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"key":"10.3233\/JAD-210614_ref39","first-page":"748","article-title":"Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition","volume":"140","author":"Pontecorvo","year":"2017","journal-title":"Brain"},{"key":"10.3233\/JAD-210614_ref40","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mcn.2018.12.001","article-title":"Biomarkers for tau pathology","volume":"97","author":"Sch\u00f6ll","year":"2019","journal-title":"Mol Cell Neurosci"},{"key":"10.3233\/JAD-210614_ref41","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jalz.2018.12.001","article-title":"Predicting diagnosis and cognition with 18 F-AV-1451 tau PET and structural MRI in Alzheimer\u2019s disease","volume":"15","author":"Mattsson","year":"2019","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-210614_ref42","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1212\/WNL.0000000000002892","article-title":"Tau PET in Alzheimer disease and mild cognitive impairment","volume":"87","author":"Cho","year":"2016","journal-title":"Neurology"},{"key":"10.3233\/JAD-210614_ref43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neurobiolaging.2018.01.024","article-title":"Longitudinal and cross-sectional structural magnetic resonance imaging correlates of AV-1451 uptake","volume":"66","author":"Das","year":"2018","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-210614_ref44","doi-asserted-by":"crossref","first-page":"eaau5732","DOI":"10.1126\/scitranslmed.aau5732","article-title":"Prospective longitudinal atrophy in Alzheimer\u2019s disease correlates with the intensity and topography of baseline tau-PET","volume":"12","author":"La Joie","year":"2020","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-210614_ref45","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.1021\/acschemneuro.9b00326","article-title":"Identification of AV-1451 as a weak, nonselective inhibitor of monoamine oxidase","volume":"10","author":"Drake","year":"2019","journal-title":"ACS Chem Neurosci"},{"key":"10.3233\/JAD-210614_ref46","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/mds.27271","article-title":"The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases","volume":"33","author":"Vermeiren","year":"2018","journal-title":"Mov Disord"},{"key":"10.3233\/JAD-210614_ref47","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuron.2020.09.042","article-title":"High-contrast in vivo imaging of tau pathologies in Alzheimer\u2019s and non-Alzheimer\u2019s disease tauopathies","volume":"109","author":"Tagai","year":"2021","journal-title":"Neuron"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-210614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:07:12Z","timestamp":1777370832000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-210614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":46,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-210614","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}