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There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired helical filament (PHF)-tau aggregates in Alzheimer (AD) brains but relatively low affinity for tau lesions in other tauopathies like temporal lobal degeneration (FTLD)-tau, progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). Little is known, however, about the binding profile of this ligand to the tau-containing lesions of CTE.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To study the binding properties of [<jats:sup>18<\/jats:sup>F]-AV-1451 on pathologically confirmed CTE postmortem brain tissue samples.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed [<jats:sup>18<\/jats:sup>F]-AV-1451 phosphor screen and high resolution autoradiography, quantitative tau measurements by immunohistochemistry and Western blot and tau seeding activity assays in brain blocks containing hippocampus, superior temporal cortex, superior frontal cortex, inferior parietal cortex and occipital cortex from 5 cases of CTE, across the stages of disease: stage II-III (<jats:italic>n<\/jats:italic>\u2009=\u20091), stage III (<jats:italic>n<\/jats:italic>\u2009=\u20093), and stage IV (<jats:italic>n<\/jats:italic>\u2009=\u20091). Importantly, low or no concomitant classic AD pathology was present in these brains.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Despite the presence of abundant tau aggregates in multiple regions in all CTE brains, only faint or no [<jats:sup>18<\/jats:sup>F]-AV-1451 binding signal could be detected by autoradiography. The only exception was the presence of a strong signal confined to the region of the choroid plexus and the meninges in two of the five cases. Tau immunostaining and Thioflavin-S staining ruled out the presence of tau aggregates in those regions. High resolution nuclear emulsion autoradiography revealed the presence of leptomeningeal melanocytes as the histologic source of this <jats:italic>off-target<\/jats:italic> binding. Levels of abnormally hyperphosphorylated tau species, as detected by Western Blotting, and tau seeding activity were both found to be lower in extracts from cases CTE when compared to AD.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in CTE. The existence of disease-specific tau conformations may likely explain the differential binding affinity of this tracer for tau lesions in different tauopathies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40478-019-0808-1","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T11:09:06Z","timestamp":1572260946000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["[18F]-AV-1451 binding profile in chronic traumatic encephalopathy: a postmortem case series"],"prefix":"10.1186","volume":"7","author":[{"given":"Marta","family":"Marqui\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinthya","family":"Ag\u00fcero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana C.","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Villarejo-Galende","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prianca","family":"Ramanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Siao Tick","family":"Chong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nil","family":"S\u00e1ez-Calveras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel E.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eline E.","family":"Verwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally Ji Who","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maeva","family":"Dhaynaut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor E.","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann C.","family":"McKee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew P.","family":"Frosch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-2075","authenticated-orcid":false,"given":"Teresa","family":"G\u00f3mez-Isla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"808_CR1","doi-asserted-by":"publisher","first-page":"338ra366","DOI":"10.1126\/scitranslmed.aaf2362","volume":"8","author":"MR Brier","year":"2016","unstructured":"Brier MR, Gordon B, Friedrichsen K, McCarthy J, Stern A, Christensen J, Owen C, Aldea P, Su Y, Hassenstab J, Cairns NJ, Holtzman DM, Fagan AM, Morris JC, Benzinger TL, Ances BM (2016) Tau and Abeta imaging, CSF measures, and cognition in Alzheimer's disease. 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Marta Marqui\u00e9 currently works at Fundaci\u00f3 ACE Institut Catal\u00e0 de Neuroci\u00e8ncies Aplicades \u2013 Universitat Internacional de Catalunya in Barcelona, Spain.Cinthya Ag\u00fcero received research funding from NIH grant AG036694 and AG061206.Ana C. Amaral received research funding from NIH grant AG036694 and AG061206. Alberto Villarejo-Galende received research funding from the Instituto de Salud Carlos III (BA17\/00035).Prianca Ramanan received research funding from NIH grant AG036694 and AG061206. Michael Siao Tick Chong received research funding from NIH grant AG036694.Eline Verwer received research funding from the Society of Nuclear Medicine and Molecular Imaging Education and Research Foundation.Sally Ji Who Kim received research funding from NIH grant T32\u2009EB013180.Keith A. Johnson received research funding from NIH grants R01 EB014894, R21 AG038994, R01 AG026484, R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435 and R01 AG037497 and the Alzheimer\u2019s Association grant ZEN-10-174210\u2009K.Ann C. McKee received research funding from NIH grants R01 AG062348, RO1 AG057902, P30-AG13846, U01 NS086659, and the Nick and Lynn Buoniconti Foundation, Andlinger Foundation, National Football League and WWE.Matthew P. Frosch received research funding from NIH grants AG005134 and AG061206. Teresa G\u00f3mez-Isla received research funding from NIH grants AG005134, AG036694 and AG061206. Teresa G\u00f3mez-Isla participated as speaker in an Eli Lilly and Company sponsored educational symposium and serves in an Eli Lilly Data Monitoring Committee. Eli Lilly and Company currently owns Avid, the company that created AV-1451.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"164"}}