TY - JOUR
T1 - Regional Distribution, Asymmetry, and Clinical Correlates of Tau Uptake on [18F]AV-1451 PET in Atypical Alzheimer's Disease
AU - Tetzloff, Katerina A.
AU - Graff-Radford, Jonathan
AU - Martin, Peter R.
AU - Tosakulwong, Nirubol
AU - Machulda, Mary M.
AU - Duffy, Joseph R.
AU - Clark, Heather M.
AU - Senjem, Matthew L.
AU - Schwarz, Christopher G.
AU - Spychalla, Anthony J.
AU - Drubach, Daniel A.
AU - Jack, Clifford R.
AU - Lowe, Val J.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Funding Information:
In summary, this study demonstrates that tau is densely and diffusely present throughout the majority of cortical regions in both PCA and lvPPA. Even so, the findings of this study show that tau-PET scans have potential to distinguish different types of atypical AD variants. Particularly, PCA and lvPPA can be distinguished by the amount of tau uptake This study was funded by NIH grants R01-AG50603, R21-NS94684, and U01 AG006786 as well as The Elsie and Marvin Dekelboum Family Foundation. We would like to thank Drs. Ronald Petersen and David Knopman for providing data from the healthy control subjects. We would also like to thank AVID Radiopharmaceuticals for their support in supplying AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.
Funding Information:
This study was funded by NIH grants R01-AG50603, R21-NS94684, and U01 AG006786 as well as The Elsie and Marvin Dekelboum Family Foundation. We would like to thank Drs. Ronald Petersen and David Knopman for providing data from the healthy control subjects. We would also like to thank AVID Radiopharmaceuticals for their support in supplying AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.
Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Background: Despite common pathology, Alzheimer's disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. Objective: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA). Methods: Eighteen PCA and 19 lvPPA subjects that showed amyloid-β deposition on PET underwent tau-PET imaging with [18F]AV-1451. Group comparisons of tau uptake in PCA and lvPPA were performed using voxel-level and regional-level analyses. We also assessed the degree of lobar tau asymmetry and correlated regional tau uptake to age and performance on clinical evaluations. Results: Both syndromes showed diffuse tau uptake throughout all cortical regions, although PCA showed greater uptake in occipital regions compared to lvPPA, and lvPPA showed greater uptake in left frontal and temporal regions compared to PCA. While lvPPA showed predominant left-asymmetric tau deposition, PCA was more bilateral. Younger subjects showed greater tau uptake bilaterally in frontal and parietal lobes than older subjects, and sentence repetition, Boston naming test, simultanagnosia, and visuoperceptual function showed specific regional tau correlates. Conclusion: Tau deposition is closely related to clinical presentation in atypical AD with age playing a role in determining the degree of cortical tau deposition.
AB - Background: Despite common pathology, Alzheimer's disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. Objective: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA). Methods: Eighteen PCA and 19 lvPPA subjects that showed amyloid-β deposition on PET underwent tau-PET imaging with [18F]AV-1451. Group comparisons of tau uptake in PCA and lvPPA were performed using voxel-level and regional-level analyses. We also assessed the degree of lobar tau asymmetry and correlated regional tau uptake to age and performance on clinical evaluations. Results: Both syndromes showed diffuse tau uptake throughout all cortical regions, although PCA showed greater uptake in occipital regions compared to lvPPA, and lvPPA showed greater uptake in left frontal and temporal regions compared to PCA. While lvPPA showed predominant left-asymmetric tau deposition, PCA was more bilateral. Younger subjects showed greater tau uptake bilaterally in frontal and parietal lobes than older subjects, and sentence repetition, Boston naming test, simultanagnosia, and visuoperceptual function showed specific regional tau correlates. Conclusion: Tau deposition is closely related to clinical presentation in atypical AD with age playing a role in determining the degree of cortical tau deposition.
KW - Aphasia
KW - dementia
KW - neuroimaging
KW - positron emission tomography
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U2 - 10.3233/JAD-170740
DO - 10.3233/JAD-170740
M3 - Article
C2 - 29614676
AN - SCOPUS:85044841641
SN - 1387-2877
VL - 62
SP - 1713
EP - 1724
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -