{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:47:36Z","timestamp":1770742056446,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Association","award":["NIRG-394284"],"award-info":[{"award-number":["NIRG-394284"]}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["AZ160106"],"award-info":[{"award-number":["AZ160106"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009670","name":"National Alliance for Research on Schizophrenia and Depression","doi-asserted-by":"publisher","award":["27565"],"award-info":[{"award-number":["27565"]}],"id":[{"id":"10.13039\/100009670","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-107090RA-100"],"award-info":[{"award-number":["PID2019-107090RA-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RYC-2017-21879"],"award-info":[{"award-number":["RYC-2017-21879"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01557"],"award-info":[{"award-number":["PI18\/01557"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002878","name":"Consejer\u00eda de Econom\u00eda, Innovaci\u00f3n, Ciencia y Empleo, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["P18-RT-2233"],"award-info":[{"award-number":["P18-RT-2233"]}],"id":[{"id":"10.13039\/501100002878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002878","name":"Consejer\u00eda de Econom\u00eda, Innovaci\u00f3n, Ciencia y Empleo, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["UMA18-FEDERJA-211"],"award-info":[{"award-number":["UMA18-FEDERJA-211"]}],"id":[{"id":"10.13039\/501100002878","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer\u2019s disease (AD), NFTs are accompanied by extracellular amyloid-beta (A\u03b2), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. 18F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer 18F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo 18F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that 18F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.<\/jats:p>","DOI":"10.3390\/diagnostics11101874","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T08:09:32Z","timestamp":1634026172000},"page":"1874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Longitudinal Assessment of Tau-Associated Pathology by 18F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-0889","authenticated-orcid":false,"given":"Ines","family":"Moreno-Gonzalez","sequence":"first","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"},{"name":"Department of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, Spain"},{"name":"Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERBED), 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"George A.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3451-3299","authenticated-orcid":false,"given":"Omar","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-7735","authenticated-orcid":false,"given":"Nazaret","family":"Gamez","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"},{"name":"Department of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan E.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jose","family":"Fernandez-Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, Spain"},{"name":"Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERBED), 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-6152","authenticated-orcid":false,"given":"Antonia","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, Spain"},{"name":"Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERBED), 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0676-002X","authenticated-orcid":false,"given":"Paul E.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2020). 2020 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 14, 367\u2013429."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-pathmechdis-012418-012936","article-title":"Molecular Pathogenesis of the Tauopathies","volume":"14","author":"Halliday","year":"2019","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.brainresbull.2016.08.018","article-title":"Tau and tauopathies","volume":"126","author":"Arendt","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1460-9568.2006.05226.x","article-title":"Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration","volume":"25","author":"Wang","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","article-title":"Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases","volume":"21","author":"Soto","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.semcdb.2011.04.002","article-title":"Misfolded protein aggregates: Mechanisms, structures and potential for disease transmission","volume":"22","author":"Soto","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1212\/WNL.0b013e3182704056","article-title":"Injury markers predict time to dementia in subjects with MCI and amyloid pathology","volume":"79","author":"Vos","year":"2012","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1159\/000106969","article-title":"Evidence of Blood-Cerebrospinal Fluid-Barrier Impairment in a Subgroup of Patients with Dementia of the Alzheimer Type and Major Depression: A Possible Indicator for Immunoactivation","volume":"6","author":"Hampel","year":"1995","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological staging of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/WCO.0b013e32835a3432","article-title":"Where, when, and in what form does sporadic Alzheimer\u2019s disease begin?","volume":"25","author":"Braak","year":"2012","journal-title":"Curr. Opin. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41380-018-0342-8","article-title":"Tau PET imaging in neurodegenerative tauopathies\u2014still a challenge","volume":"24","author":"Leuzy","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ishiki, A., Okamura, N., Furukawa, K., Furumoto, S., Harada, R., Tomita, N., Hiraoka, K., Watanuki, S., Ishikawa, Y., and Tago, T. (2015). Longitudinal Assessment of Tau Pathology in Patients with Alzheimer\u2019s Disease Using [18F]THK-5117 Positron Emission Tomography. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140311"},{"key":"ref_16","first-page":"1","article-title":"Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain","volume":"9","author":"Ng","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.2967\/jnumed.117.197426","article-title":"Correlations of 18F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease","volume":"59","author":"Harada","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Edwards, G., Gamez, N., Armijo, E., Kramm, C., Morales, R., Taylor-Presse, K., Schulz, P.E., Soto, C., and Moreno-Gonzalez, I. (2019). Peripheral Delivery of Neural Precursor Cells Ameliorates Parkinson\u2019s Disease-Associated Pathology. Cells, 8.","DOI":"10.3390\/cells8111359"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0892-0362(90)90061-G","article-title":"Effects of MPTP on locomotor activity in mice","volume":"12","author":"Colotla","year":"1990","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/mp.2016.230","article-title":"Molecular interaction between type 2 diabetes and Alzheimer\u2019s disease through cross-seeding of protein misfolding","volume":"22","author":"Edwards","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/neu.2018.6348","article-title":"Traumatic Brain Injury Induces Tau Aggregation and Spreading","volume":"37","author":"Edwards","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00401-007-0200-2","article-title":"Silver diagnosis in neuropathology: Principles, practice and revised interpretation","volume":"113","author":"Uchihara","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-017-0231-7","article-title":"Practical considerations for choosing a mouse model of Alzheimer\u2019s disease","volume":"12","author":"Jankowsky","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.arr.2017.03.002","article-title":"In vivo tau PET imaging in dementia: Pathophysiology, radiotracer quantification, and a systematic review of clinical findings","volume":"36","author":"Hall","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9340","DOI":"10.1523\/JNEUROSCI.22-21-09340.2002","article-title":"Abundant tau filaments and nonapoptotic neuro-degeneration in mice transgenic for human P301S tau","volume":"22","author":"Allen","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1001\/jamaneurol.2017.2822","article-title":"Kinetics of Human Mutant Tau Prion Formation in the Brains of 2 Transgenic Mouse Lines","volume":"74","author":"Woerman","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.nbd.2014.01.007","article-title":"Synergistic effects of amyloid-beta and wild-type human tau on dendritic spine loss in a floxed double transgenic model of Alzheimer\u2019s disease","volume":"64","author":"Chabrier","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1046\/j.1471-4159.2003.01879.x","article-title":"Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms","volume":"86","author":"Andorfer","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.tips.2010.06.002","article-title":"Small-animal positron emission tomography as a tool for neuropharmacology","volume":"31","author":"Lancelot","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1001\/jamaneurol.2013.1453","article-title":"Mechanisms of Protein Seeding in Neurodegenerative Diseases","volume":"70","author":"Walker","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4161\/pri.3.2.8754","article-title":"The expanding realm of prion phenomena in neurodegenerative disease","volume":"3","author":"Frost","year":"2009","journal-title":"Prion"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E4376","DOI":"10.1073\/pnas.1411649111","article-title":"Proteopathic tau seeding predicts tauopathy in vivo","volume":"111","author":"Holmes","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12883-018-1115-3","article-title":"[18F]THK5351 PET imaging in early-stage semantic variant primary progressive aphasia: A report of two cases and a literature review","volume":"18","author":"Kobayashi","year":"2018","journal-title":"BMC Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3988\/jcn.2020.16.2.202","article-title":"[18F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment","volume":"16","author":"Jeong","year":"2020","journal-title":"J. Clin. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40478-018-0637-7","article-title":"Different tau species lead to heterogeneous tau pathology propagation and misfolding","volume":"6","author":"Dujardin","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"208","DOI":"10.2967\/jnumed.115.164848","article-title":"18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease","volume":"57","author":"Harada","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.nucmedbio.2020.10.002","article-title":"Synthesis and evaluation of 2-pyrrolopyridinylquinoline derivatives as selective tau PET tracers for the diagnosis of Alzheimer\u2019s disease","volume":"93","author":"Lerdsirisuk","year":"2021","journal-title":"Nucl. Med. Biol."},{"key":"ref_39","first-page":"1","article-title":"Combination of automated brain volumetry on MRI and quantitative tau deposition on THK-5351 PET to support diagnosis of Alzheimer\u2019s disease","volume":"11","author":"Kim","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4103\/wjnm.WJNM_50_20","article-title":"Analysis of amyloid and tau deposition in Alzheimer\u2019s disease using11C-Pittsburgh compound B and18F-THK 5351 positron emission tomography imaging","volume":"20","author":"Chanisa","year":"2021","journal-title":"World J. Nucl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"615467","DOI":"10.3389\/fnagi.2020.615467","article-title":"Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis","volume":"12","author":"Lee","year":"2021","journal-title":"Front. Aging Neurosci."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:11:52Z","timestamp":1760166712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["diagnostics11101874"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11101874","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}