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Abstract
Objective To assess whether Alzheimer disease (AD) clinical presentation and APOE4 relate to the burden and topography of β-amyloid (Aβ) and tau pathologies using in vivo PET imaging.
Methods We studied 119 Aβ-positive symptomatic patients aged 48–95 years, including 29 patients with logopenic variant primary progressive aphasia (lvPPA) and 21 with posterior cortical atrophy (PCA). Pittsburgh compound B (PiB)–Aβ and flortaucipir (tau)–PET standardized uptake value ratio (SUVR) images were created. General linear models assessed relationships between demographic/clinical variables (phenotype, age), APOE4, and PET (including global cortical and voxelwise SUVR values) while controlling for disease severity using the Clinical Dementia Rating Sum of Boxes.
Results PiB-PET binding showed a widespread cortical distribution with subtle differences across phenotypes and was unrelated to demographic/clinical variables or APOE4. Flortaucipir-PET was commonly elevated in temporoparietal regions, but showed marked phenotype-associated differences, with higher binding observed in occipito-parietal areas for PCA, in left temporal and inferior frontal for lvPPA, and in medial temporal areas for other AD. Cortical flortaucipir-PET binding was higher in younger patients across phenotypes (r = −0.63, 95% confidence interval [CI] −0.72, −0.50), especially in parietal and dorsal prefrontal cortices. The presence of APOE4 was associated with a focal medial temporal flortaucipir-SUVR increase, controlling for all other variables (entorhinal: + 0.310 SUVR, 95% CI 0.091, 0.530).
Conclusions Clinical phenotypes are associated with differential patterns of tau but not amyloid pathology. Older age and APOE4 are not only risk factors for AD but also seem to affect disease expression by promoting a more medial temporal lobe–predominant pattern of tau pathology.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- CDR=
- Clinical Dementia Rating;
- CDR-SB=
- Clinical Dementia Rating scale, Sum of Boxes;
- CI=
- confidence interval;
- FTP=
- flortaucipir;
- FWE=
- familywise error;
- GLM=
- General Linear Model;
- GM=
- gray matter;
- LBNL=
- Lawrence Berkeley National Laboratory;
- lvPPA=
- logopenic variant primary progressive aphasia;
- MTL=
- medial temporal lobe;
- PCA=
- posterior cortical atrophy;
- PiB=
- Pittsburgh compound B;
- PVC=
- partial volume correction;
- SUVR=
- standard uptake value ratio;
- UCSF=
- University of California San Francisco;
- VBM=
- voxel-based morphometry
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 191
- Received March 23, 2020.
- Accepted in final form September 11, 2020.
- © 2020 American Academy of Neurology
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