frontotemporal dementia

apoe

cognitive impairment

patients ad

ad risk

cortical thinning

apoe genotype

amyloid plaques

glucose metabolism

Neurology

<h3>Objective</h3> To assess whether Alzheimer disease (AD) clinical presentation and <i>APOE4</i> relate to the burden and topography of β-amyloid (Aβ) and tau pathologies using in vivo PET imaging. <h3>Methods</h3> 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), <i>APOE4</i>, and PET (including global cortical and voxelwise SUVR values) while controlling for disease severity using the Clinical Dementia Rating Sum of Boxes. <h3>Results</h3> PiB-PET binding showed a widespread cortical distribution with subtle differences across phenotypes and was unrelated to demographic/clinical variables or <i>APOE4</i>. 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 (<i>r</i> = −0.63, 95% confidence interval [CI] −0.72, −0.50), especially in parietal and dorsal prefrontal cortices. The presence of <i>APOE4</i> 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). <h3>Conclusions</h3> Clinical phenotypes are associated with differential patterns of tau but not amyloid pathology. Older age and <i>APOE4</i> 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.

Association of APOE4 and Clinical Variability in Alzheimer Disease With the Pattern of Tau- and Amyloid-PET