Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
Abstract 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...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-06-01
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| Series: | EJNMMI Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13550-020-00653-x |
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| author | Michael J. Pontecorvo C. Dirk Keene Thomas G. Beach Thomas J. Montine Anupa K. Arora Michael D. Devous Michael Navitsky Ian Kennedy Abhinay D. Joshi Ming Lu Geidy E. Serrano Lucia I. Sue Anthony J. Intorcia Shannon E. Rose Angela Wilson Leanne Hellstern Natalie Coleman Matthew Flitter Patricia Aldea Adam S. Fleisher Mark A. Mintun Andrew Siderowf |
| author_facet | Michael J. Pontecorvo C. Dirk Keene Thomas G. Beach Thomas J. Montine Anupa K. Arora Michael D. Devous Michael Navitsky Ian Kennedy Abhinay D. Joshi Ming Lu Geidy E. Serrano Lucia I. Sue Anthony J. Intorcia Shannon E. Rose Angela Wilson Leanne Hellstern Natalie Coleman Matthew Flitter Patricia Aldea Adam S. Fleisher Mark A. Mintun Andrew Siderowf |
| author_sort | Michael J. Pontecorvo |
| collection | DOAJ |
| description | Abstract 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 [18F]. 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 Aβ1-42 were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ1-42 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 |
| first_indexed | 2024-12-19T03:00:32Z |
| format | Article |
| id | doaj.art-c560e3ec351446138c0423bbda783d83 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-19T03:00:32Z |
| publishDate | 2020-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-c560e3ec351446138c0423bbda783d832022-12-21T20:38:13ZengSpringerOpenEJNMMI Research2191-219X2020-06-0110111010.1186/s13550-020-00653-xComparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological studyMichael J. Pontecorvo0C. Dirk Keene1Thomas G. Beach2Thomas J. Montine3Anupa K. Arora4Michael D. Devous5Michael Navitsky6Ian Kennedy7Abhinay D. Joshi8Ming Lu9Geidy E. Serrano10Lucia I. Sue11Anthony J. Intorcia12Shannon E. Rose13Angela Wilson14Leanne Hellstern15Natalie Coleman16Matthew Flitter17Patricia Aldea18Adam S. Fleisher19Mark A. Mintun20Andrew Siderowf21Avid RadiopharmaceuticalsDepartment of Pathology, University of WashingtonCivin Laboratory for Neuropathology, Banner Sun Health Research InstituteDepartment of Pathology, Stanford UniversityAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsCivin Laboratory for Neuropathology, Banner Sun Health Research InstituteCivin Laboratory for Neuropathology, Banner Sun Health Research InstituteCivin Laboratory for Neuropathology, Banner Sun Health Research InstituteDepartment of Pathology, University of WashingtonDepartment of Pathology, University of WashingtonDepartment of Pathology, University of WashingtonDepartment of Pathology, University of WashingtonAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAvid RadiopharmaceuticalsAbstract 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 [18F]. 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 Aβ1-42 were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ1-42 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=1http://link.springer.com/article/10.1186/s13550-020-00653-xFlortaucipir[18F]-AV-1451PETAlzheimer’sTauNFT |
| spellingShingle | Michael J. Pontecorvo C. Dirk Keene Thomas G. Beach Thomas J. Montine Anupa K. Arora Michael D. Devous Michael Navitsky Ian Kennedy Abhinay D. Joshi Ming Lu Geidy E. Serrano Lucia I. Sue Anthony J. Intorcia Shannon E. Rose Angela Wilson Leanne Hellstern Natalie Coleman Matthew Flitter Patricia Aldea Adam S. Fleisher Mark A. Mintun Andrew Siderowf Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study EJNMMI Research Flortaucipir [18F]-AV-1451 PET Alzheimer’s Tau NFT |
| 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 | Flortaucipir [18F]-AV-1451 PET Alzheimer’s Tau NFT |
| url | http://link.springer.com/article/10.1186/s13550-020-00653-x |
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