Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology
Abstract Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitati...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-022-01412-w |
| _version_ | 1811215465569058816 |
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| author | Adam Martersteck Ivan Ayala Daniel T. Ohm Callen Spencer Christina Coventry Sandra Weintraub Eileen H. Bigio M. -Marsel Mesulam Changiz Geula Emily Rogalski |
| author_facet | Adam Martersteck Ivan Ayala Daniel T. Ohm Callen Spencer Christina Coventry Sandra Weintraub Eileen H. Bigio M. -Marsel Mesulam Changiz Geula Emily Rogalski |
| author_sort | Adam Martersteck |
| collection | DOAJ |
| description | Abstract Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitative relationship between regional binding of in vivo 18F-florbetapir amyloid PET and 18F-flortaucipir tau PET with postmortem stereological counts of amyloid plaques and neurofibrillary tangles (NFT) in a case of primary progressive aphasia (PPA) with ADNC, where neurodegeneration asymmetrically targets the left hemisphere. Beginning 2 years prior to death, a 63-year-old right-handed man presenting with agrammatic variant PPA underwent a florbetapir and flortaucpir PET scan, and neuropsychological assessments and magnetic resonance imaging sessions every 6 months. Florbetapir and flortaucpir PET standard uptake value ratios (SUVRs) were quantified from 8 left and right hemisphere brain regions with stereological quantification of amyloid plaques and NFTs from corresponding postmortem sections. Pearson’s correlations and measures of asymmetry were used to examine relationships between imaging and autopsy measurements. The three visits prior to death revealed decline of language measures, with marked progression of atrophy. Florbetapir PET presented with an atypical focal pattern of uptake and showed a significant positive correlation with postmortem amyloid plaque density across the 8 regions (r = 0.92; p = 0.001). Flortaucipir PET had a left-lateralized distribution and showed a significant positive correlation with NFT density (r = 0.78; p = 0.023). Flortaucipir PET and NFT density indicated a medial temporal lobe sparing presentation of ADNC, demonstrating that AD does not always target the medial temporal lobe. This study adds additional evidence, in a non-amnestic phenotype of ADNC, that there is a strong correlation between AD PET biomarkers, florbetapir and flortaucipir, with quantitative neuropathology. The atypical and focal presentation of plaque density and florbetapir PET uptake suggests not all amyloid pathology presents as diffuse across neocortex. |
| first_indexed | 2024-04-12T06:23:02Z |
| format | Article |
| id | doaj.art-dee5d657b80b4aea9235b2ab51caffdc |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-12T06:23:02Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-dee5d657b80b4aea9235b2ab51caffdc2022-12-22T03:44:16ZengBMCActa Neuropathologica Communications2051-59602022-08-0110111210.1186/s40478-022-01412-wFocal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathologyAdam Martersteck0Ivan Ayala1Daniel T. Ohm2Callen Spencer3Christina Coventry4Sandra Weintraub5Eileen H. Bigio6M. -Marsel Mesulam7Changiz Geula8Emily Rogalski9Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineMesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University (NU) Feinberg School of MedicineAbstract Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitative relationship between regional binding of in vivo 18F-florbetapir amyloid PET and 18F-flortaucipir tau PET with postmortem stereological counts of amyloid plaques and neurofibrillary tangles (NFT) in a case of primary progressive aphasia (PPA) with ADNC, where neurodegeneration asymmetrically targets the left hemisphere. Beginning 2 years prior to death, a 63-year-old right-handed man presenting with agrammatic variant PPA underwent a florbetapir and flortaucpir PET scan, and neuropsychological assessments and magnetic resonance imaging sessions every 6 months. Florbetapir and flortaucpir PET standard uptake value ratios (SUVRs) were quantified from 8 left and right hemisphere brain regions with stereological quantification of amyloid plaques and NFTs from corresponding postmortem sections. Pearson’s correlations and measures of asymmetry were used to examine relationships between imaging and autopsy measurements. The three visits prior to death revealed decline of language measures, with marked progression of atrophy. Florbetapir PET presented with an atypical focal pattern of uptake and showed a significant positive correlation with postmortem amyloid plaque density across the 8 regions (r = 0.92; p = 0.001). Flortaucipir PET had a left-lateralized distribution and showed a significant positive correlation with NFT density (r = 0.78; p = 0.023). Flortaucipir PET and NFT density indicated a medial temporal lobe sparing presentation of ADNC, demonstrating that AD does not always target the medial temporal lobe. This study adds additional evidence, in a non-amnestic phenotype of ADNC, that there is a strong correlation between AD PET biomarkers, florbetapir and flortaucipir, with quantitative neuropathology. The atypical and focal presentation of plaque density and florbetapir PET uptake suggests not all amyloid pathology presents as diffuse across neocortex.https://doi.org/10.1186/s40478-022-01412-wAlzheimer diseasePrimary progressive aphasiaAmyloidTauPositron emission tomographyStereology |
| spellingShingle | Adam Martersteck Ivan Ayala Daniel T. Ohm Callen Spencer Christina Coventry Sandra Weintraub Eileen H. Bigio M. -Marsel Mesulam Changiz Geula Emily Rogalski Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology Acta Neuropathologica Communications Alzheimer disease Primary progressive aphasia Amyloid Tau Positron emission tomography Stereology |
| title | Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology |
| title_full | Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology |
| title_fullStr | Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology |
| title_full_unstemmed | Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology |
| title_short | Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology |
| title_sort | focal amyloid and asymmetric tau in an imaging to autopsy case of clinical primary progressive aphasia with alzheimer disease neuropathology |
| topic | Alzheimer disease Primary progressive aphasia Amyloid Tau Positron emission tomography Stereology |
| url | https://doi.org/10.1186/s40478-022-01412-w |
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