Cargando…

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study

BACKGROUND: The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy. METHODS: Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life,...

Descripción completa

Detalles Bibliográficos
Autores principales: Pontecorvo, Michael J., Keene, C. Dirk, Beach, Thomas G., Montine, Thomas J., Arora, Anupa K., Devous, Michael D., Navitsky, Michael, Kennedy, Ian, Joshi, Abhinay D., Lu, Ming, Serrano, Geidy E., Sue, Lucia I., Intorcia, Anthony J., Rose, Shannon E., Wilson, Angela, Hellstern, Leanne, Coleman, Natalie, Flitter, Matthew, Aldea, Patricia, Fleisher, Adam S., Mintun, Mark A., Siderowf, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295920/
https://www.ncbi.nlm.nih.gov/pubmed/32542468
http://dx.doi.org/10.1186/s13550-020-00653-x
_version_ 1783546738493095936
author Pontecorvo, Michael J.
Keene, C. Dirk
Beach, Thomas G.
Montine, Thomas J.
Arora, Anupa K.
Devous, Michael D.
Navitsky, Michael
Kennedy, Ian
Joshi, Abhinay D.
Lu, Ming
Serrano, Geidy E.
Sue, Lucia I.
Intorcia, Anthony J.
Rose, Shannon E.
Wilson, Angela
Hellstern, Leanne
Coleman, Natalie
Flitter, Matthew
Aldea, Patricia
Fleisher, Adam S.
Mintun, Mark A.
Siderowf, Andrew
author_facet Pontecorvo, Michael J.
Keene, C. Dirk
Beach, Thomas G.
Montine, Thomas J.
Arora, Anupa K.
Devous, Michael D.
Navitsky, Michael
Kennedy, Ian
Joshi, Abhinay D.
Lu, Ming
Serrano, Geidy E.
Sue, Lucia I.
Intorcia, Anthony J.
Rose, Shannon E.
Wilson, Angela
Hellstern, Leanne
Coleman, Natalie
Flitter, Matthew
Aldea, Patricia
Fleisher, Adam S.
Mintun, Mark A.
Siderowf, Andrew
author_sort Pontecorvo, Michael J.
collection PubMed
description BACKGROUND: The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy. METHODS: Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [(18)F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. SUVr values were calculated for each region using a cerebellar reference region. Abnormally phosphorylated tau (Ptau) and amyloid-β (Aβ) tissue concentrations were measured for each tissue region with an antibody capture assay (Histelide) using AT8 and H31L21 antibodies respectively. RESULTS: The imaging-to-autopsy interval ranged from 4–29 days. All three subjects had intermediate to high levels of AD neuropathologic change at autopsy. Mean cortical SUVr averaged across all three subjects correlated significantly with the Ptau immunoassay (Pearson r = 0.81; p < 0.0001). When Ptau and Aβ(1-42) were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ(1-42) with flortaucipir. There was also a modest correlation between limbic (hippocampal/entorhinal and amygdala) flortaucipir SUVr and Ptau (Pearson r = 0.52; p < 0.080). There was no significant correlation between SUVr and Ptau in basal ganglia. CONCLUSIONS: The results of this pilot study support a quantitative relationship between cortical flortaucipir SUVr values and quantitative measures of Ptau at autopsy. Additional research including more cases is needed to confirm the generalizability of these results. Trial registration, NIH Clinicaltrials.gov NCT # 02516046. Registered August 27, 2015. https://clinicaltrials.gov/ct2/show/NCT02516046?term=02516046&draw=2&rank=1
format Online
Article
Text
id pubmed-7295920
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-72959202020-06-22 Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study Pontecorvo, Michael J. Keene, C. Dirk Beach, Thomas G. Montine, Thomas J. Arora, Anupa K. Devous, Michael D. Navitsky, Michael Kennedy, Ian Joshi, Abhinay D. Lu, Ming Serrano, Geidy E. Sue, Lucia I. Intorcia, Anthony J. Rose, Shannon E. Wilson, Angela Hellstern, Leanne Coleman, Natalie Flitter, Matthew Aldea, Patricia Fleisher, Adam S. Mintun, Mark A. Siderowf, Andrew EJNMMI Res Original Research BACKGROUND: The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy. METHODS: Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [(18)F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. SUVr values were calculated for each region using a cerebellar reference region. Abnormally phosphorylated tau (Ptau) and amyloid-β (Aβ) tissue concentrations were measured for each tissue region with an antibody capture assay (Histelide) using AT8 and H31L21 antibodies respectively. RESULTS: The imaging-to-autopsy interval ranged from 4–29 days. All three subjects had intermediate to high levels of AD neuropathologic change at autopsy. Mean cortical SUVr averaged across all three subjects correlated significantly with the Ptau immunoassay (Pearson r = 0.81; p < 0.0001). When Ptau and Aβ(1-42) were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ(1-42) with flortaucipir. There was also a modest correlation between limbic (hippocampal/entorhinal and amygdala) flortaucipir SUVr and Ptau (Pearson r = 0.52; p < 0.080). There was no significant correlation between SUVr and Ptau in basal ganglia. CONCLUSIONS: The results of this pilot study support a quantitative relationship between cortical flortaucipir SUVr values and quantitative measures of Ptau at autopsy. Additional research including more cases is needed to confirm the generalizability of these results. Trial registration, NIH Clinicaltrials.gov NCT # 02516046. Registered August 27, 2015. https://clinicaltrials.gov/ct2/show/NCT02516046?term=02516046&draw=2&rank=1 Springer Berlin Heidelberg 2020-06-15 /pmc/articles/PMC7295920/ /pubmed/32542468 http://dx.doi.org/10.1186/s13550-020-00653-x Text en © The Author(s) 2020 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/.
spellingShingle Original Research
Pontecorvo, Michael J.
Keene, C. Dirk
Beach, Thomas G.
Montine, Thomas J.
Arora, Anupa K.
Devous, Michael D.
Navitsky, Michael
Kennedy, Ian
Joshi, Abhinay D.
Lu, Ming
Serrano, Geidy E.
Sue, Lucia I.
Intorcia, Anthony J.
Rose, Shannon E.
Wilson, Angela
Hellstern, Leanne
Coleman, Natalie
Flitter, Matthew
Aldea, Patricia
Fleisher, Adam S.
Mintun, Mark A.
Siderowf, Andrew
Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title_full Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title_fullStr Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title_full_unstemmed Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title_short Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
title_sort comparison of regional flortaucipir pet with quantitative tau immunohistochemistry in three subjects with alzheimer’s disease pathology: a clinicopathological study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295920/
https://www.ncbi.nlm.nih.gov/pubmed/32542468
http://dx.doi.org/10.1186/s13550-020-00653-x
work_keys_str_mv AT pontecorvomichaelj comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT keenecdirk comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT beachthomasg comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT montinethomasj comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT aroraanupak comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT devousmichaeld comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT navitskymichael comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT kennedyian comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT joshiabhinayd comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT luming comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT serranogeidye comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT sueluciai comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT intorciaanthonyj comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT roseshannone comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT wilsonangela comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT hellsternleanne comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT colemannatalie comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT flittermatthew comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT aldeapatricia comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT fleisheradams comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT mintunmarka comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy
AT siderowfandrew comparisonofregionalflortaucipirpetwithquantitativetauimmunohistochemistryinthreesubjectswithalzheimersdiseasepathologyaclinicopathologicalstudy