Gray-Matter Atrophy and APOE ε4 Effects within the Default Mode Network: A Voxel-Based Morphometry Analysis of Taiwanese Alzheimer’s Disease Patients

Introduction: This study examines structural changes in the Default Mode Network (DMN) related to Alzheimer's disease (AD) using MRI data from a Taiwanese cohort. We also investigate how the APOE ε4 allele influences these regional alterations, enhancing the understanding of AD pathogenesis by highlighting crucial genetic contributions often overlooked in global research. Methods: The study included MRI data from 93 Alzheimer's patients(AD) and 77 normal controls(NC) in Taiwan. Voxel-based morphometry (VBM) and regional analyses examined gray matter differences. Comparisons, adjusted for age, sex, and total intracranial volume, were conducted using student t-tests and ANCOVA to identify whole-brain and DMN-specific changes. Results: AD patients showed significant gray matter(GM) reductions in the whole brain and DMN regions compared to healthy controls, particularly in the bilateral angular gyrus and right inferior parietal lobe. Subgroup analyses revealed that both APOE ε4 carriers and non-carriers with AD had GM reductions, but only non-carriers showed significant DMN volume differences. Conclusion : The study finds significant GM atrophy in key DMN regions linked to AD, especially in bilateral angular gyrus and right inferior parietal lobe. Although APOE ε4 carriers did not differ significantly from non-carriers, they showed broader structural changes, suggesting a role of APOE ε4 in GM degeneration. These findings underscore the importance of structural MRI for early AD detection and integrating genetic factors in future research.