Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults

Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (A beta) and APOE epsilon 4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrophy remain relatively unclear. Our aim was to uncover these effects using baseline data from 130 participants included in the Age-Well study, for whom ultra-high-resolution structural MRI, amyloid-PET and APOE epsilon 4 genotype were available. No volume differences were observed between A beta + (n = 24) and A beta- (n = 103), nor between APOE4+ (n = 35) and APOE4- (n = 95) participants. However, our analyses showed that both A beta and APOE epsilon 4 status interacted with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOE epsilon 4 status moderated the effects of age on other subregions (subiculum, ERC), suggesting a more important contribution of APOE epsilon 4 than A beta to MTL atrophy in cognitively unimpaired population. These results are crucial to develop MRI-based biomarkers to detect early AD.

Automated summary

Medial temporal lobe subregions, including the entorhinal cortex, perirhinal cortex, and hippocampal cornu ammonis (CA)1, are differentially affected in Alzheimer's disease (AD). This study investigated the relationship between amyloid (A beta) and APOE epsilon 4 with MTL atrophy using baseline data from 130 participants. The results showed an interaction between A beta and APOE epsilon 4 status with age on CA1, indicating their specific involvement in early AD-related atrophy.