Objective: To examine the influence of the APOE genotype on levels of β-amyloid (Aβ) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo.

Methods: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the 4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Aβ plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and 4 allele frequency.

Results: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both 4-positive and 4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in 4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher 4 allele frequency and stronger temporoparietal Aβ plaque deposition, independently of other confounds. No major correlation between 4 allele frequency and gray matter decrease was observed.

Conclusion: These results indicate that the 4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Aβ plaque deposition in 4-positive patients with AD compared to age-matched 4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Aβ plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.