Renaud La Joie1, Adrienne V Visani2, Orit H Lesman-Segev2, Suzanne L Baker2, Lauren Edwards2, Leonardo Iaccarino2, David N Soleimani-Meigooni2, Taylor Mellinger2, Mustafa Janabi2, Zachary A Miller2, David C Perry2, Julie Pham2, Amelia Strom2, Maria Luisa Gorno-Tempini2, Howard J Rosen2, Bruce L Miller2, William J Jagust2, Gil D Rabinovici2. 1. From the Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences (R.L.J., A.V.V., O.H.L.-V., L.E., L.I., D.N.S.-M., T.M., Z.A.M., D.C.P., J.P., A.S., M.L.G.-T., H.J.R., B.L.M., G.D.R.), and Department of Radiology and Biomedical Imaging (G.D.R.), University of California, San Francisco; Department of Diagnostic Imaging (O.H.L.-V.), Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Molecular Biophysics and Integrated Bioimaging Division (S.L.B., M.J., W.J.J., G.D.R.), Lawrence Berkeley National Laboratory; and Helen Wills Neuroscience Institute (W.J.J., G.D.R.), University of California Berkeley. Renaud.lajoie@ucsf.edu. 2. From the Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences (R.L.J., A.V.V., O.H.L.-V., L.E., L.I., D.N.S.-M., T.M., Z.A.M., D.C.P., J.P., A.S., M.L.G.-T., H.J.R., B.L.M., G.D.R.), and Department of Radiology and Biomedical Imaging (G.D.R.), University of California, San Francisco; Department of Diagnostic Imaging (O.H.L.-V.), Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Molecular Biophysics and Integrated Bioimaging Division (S.L.B., M.J., W.J.J., G.D.R.), Lawrence Berkeley National Laboratory; and Helen Wills Neuroscience Institute (W.J.J., G.D.R.), University of California Berkeley.
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.
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.
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