Association of APOE4 and clinical variability in Alzheimer disease with the pattern of tau- and amyloid-PET

Objective To assess whether Alzheimer disease (AD) clinical presentation and APOE4 relate to the burden and topography of β-amyloid and tau pathologies using in vivo PET imaging.

Methods We studied 119 β-amyloid-positive symptomatic patients aged 48–95 years, including 29 patients with logopenic variant primary progressive aphasia (lvPPA) and 21 with Posterior Cortical Atrophy (PCA). PIB- (β-amyloid) 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 scale 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 temporo-parietal 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 patients with AD. Cortical Flortaucipir-PET binding was higher in younger patients across phenotypes (r = −0.63, 95%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 MTL-predominant pattern of tau pathology.