Abstract
Background: Deposition of beta amyloid protein (Aβ) is known to be an early event that is closely associated with the pathogenesis of Alzheimer's disease (AD), along with related downstream events such as neuronal loss, neurofibrillary tangles, cortical thinning and cognitive deficits. APOE e4 allele (E4) is also known to be associated with increased risk for AD. Objectives: The goal of this study is to examine the association of Aβ deposition to cortical thickness (CoTh), in healthy control (CN), early MCI (EMCI), late MCI (LMCI) and AD stages by controlling for E4 load, both in regional and hemispheric levels, and to interpret patterns of different brain regions based on their correlation performance among the four groups. Methods: We analyzed Amyloid PET Scan, Volumetric MRI (CoTh) data from participants in the ADNIGO/ADNI2 cohort whose APOE gene information are available. Statistical analysis includes Pearson partial correlations, Analysis of Covariance (ANCOVA) with post-hoc Tukey HSD. Complete-linkage hierarchical clustering analysis was further performed to group brain regions based on their significant correlation performance. Results: 25 out of 68 regions showed significant correlation of Aβ load and CoTh at least in one diagnostic group. Furthermore, 6 main clusters were recognized based on the performance patterns of those 25 regions across 4 diagnosis groups. Conclusion: Our major finding clustered the cortical regions into 2 general groups, positive correlation in CN or AD, and negative correlation in EMCI and/or LMCI, and 6 more specific groups were then recognized, confirming the interplay between of Aβ and CoTh in the different stages of the disease.