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Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players

PURPOSE: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for d...

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Autores principales: Alosco, Michael L., Su, Yi, Stein, Thor D., Protas, Hillary, Cherry, Jonathan D., Adler, Charles H., Balcer, Laura J., Bernick, Charles, Pulukuri, Surya Vamsi, Abdolmohammadi, Bobak, Coleman, Michael J., Palmisano, Joseph N., Tripodis, Yorghos, Mez, Jesse, Rabinovici, Gil D., Marek, Kenneth L., Beach, Thomas G., Johnson, Keith A., Huber, Bertrand Russell, Koerte, Inga, Lin, Alexander P., Bouix, Sylvain, Cummings, Jeffrey L., Shenton, Martha E., Reiman, Eric M., McKee, Ann C., Stern, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816291/
https://www.ncbi.nlm.nih.gov/pubmed/36152064
http://dx.doi.org/10.1007/s00259-022-05963-x
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author Alosco, Michael L.
Su, Yi
Stein, Thor D.
Protas, Hillary
Cherry, Jonathan D.
Adler, Charles H.
Balcer, Laura J.
Bernick, Charles
Pulukuri, Surya Vamsi
Abdolmohammadi, Bobak
Coleman, Michael J.
Palmisano, Joseph N.
Tripodis, Yorghos
Mez, Jesse
Rabinovici, Gil D.
Marek, Kenneth L.
Beach, Thomas G.
Johnson, Keith A.
Huber, Bertrand Russell
Koerte, Inga
Lin, Alexander P.
Bouix, Sylvain
Cummings, Jeffrey L.
Shenton, Martha E.
Reiman, Eric M.
McKee, Ann C.
Stern, Robert A.
author_facet Alosco, Michael L.
Su, Yi
Stein, Thor D.
Protas, Hillary
Cherry, Jonathan D.
Adler, Charles H.
Balcer, Laura J.
Bernick, Charles
Pulukuri, Surya Vamsi
Abdolmohammadi, Bobak
Coleman, Michael J.
Palmisano, Joseph N.
Tripodis, Yorghos
Mez, Jesse
Rabinovici, Gil D.
Marek, Kenneth L.
Beach, Thomas G.
Johnson, Keith A.
Huber, Bertrand Russell
Koerte, Inga
Lin, Alexander P.
Bouix, Sylvain
Cummings, Jeffrey L.
Shenton, Martha E.
Reiman, Eric M.
McKee, Ann C.
Stern, Robert A.
author_sort Alosco, Michael L.
collection PubMed
description PURPOSE: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. METHODS: Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). RESULTS: Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. CONCLUSIONS: Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
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spelling pubmed-98162912023-01-07 Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players Alosco, Michael L. Su, Yi Stein, Thor D. Protas, Hillary Cherry, Jonathan D. Adler, Charles H. Balcer, Laura J. Bernick, Charles Pulukuri, Surya Vamsi Abdolmohammadi, Bobak Coleman, Michael J. Palmisano, Joseph N. Tripodis, Yorghos Mez, Jesse Rabinovici, Gil D. Marek, Kenneth L. Beach, Thomas G. Johnson, Keith A. Huber, Bertrand Russell Koerte, Inga Lin, Alexander P. Bouix, Sylvain Cummings, Jeffrey L. Shenton, Martha E. Reiman, Eric M. McKee, Ann C. Stern, Robert A. Eur J Nucl Med Mol Imaging Original Article PURPOSE: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. METHODS: Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). RESULTS: Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. CONCLUSIONS: Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed. Springer Berlin Heidelberg 2022-09-24 2023 /pmc/articles/PMC9816291/ /pubmed/36152064 http://dx.doi.org/10.1007/s00259-022-05963-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Alosco, Michael L.
Su, Yi
Stein, Thor D.
Protas, Hillary
Cherry, Jonathan D.
Adler, Charles H.
Balcer, Laura J.
Bernick, Charles
Pulukuri, Surya Vamsi
Abdolmohammadi, Bobak
Coleman, Michael J.
Palmisano, Joseph N.
Tripodis, Yorghos
Mez, Jesse
Rabinovici, Gil D.
Marek, Kenneth L.
Beach, Thomas G.
Johnson, Keith A.
Huber, Bertrand Russell
Koerte, Inga
Lin, Alexander P.
Bouix, Sylvain
Cummings, Jeffrey L.
Shenton, Martha E.
Reiman, Eric M.
McKee, Ann C.
Stern, Robert A.
Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title_full Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title_fullStr Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title_full_unstemmed Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title_short Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
title_sort associations between near end-of-life flortaucipir pet and postmortem cte-related tau neuropathology in six former american football players
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816291/
https://www.ncbi.nlm.nih.gov/pubmed/36152064
http://dx.doi.org/10.1007/s00259-022-05963-x
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