Studying APOE epsilon 4 Allele Dose Effects with a Univariate Morphometry Biomarker

Background: A univariate neurodegeneration biomarker (UNB) based on MRI with strong statistical discrimination power would be highly desirable for studying hippocampal surface morphological changes associated with APOE epsilon 4 genetic risk for AD in the cognitively unimpaired (CU) population. However, existing UNB work either fails to model large group variances or does not capture AD induced changes. Objective: We proposed a subspace decomposition method capable of exploiting a UNB to represent the hippocampal morphological changes related to the APOE epsilon 4 dose effects among the longitudinal APOE epsilon 4 homozygotes (HM, N= 30), heterozygotes (HT, N= 49) and non-carriers (NC, N= 61). Methods: Rank minimization mechanism combined with sparse constraint considering the local continuity of the hippocampal atrophy regions is used to extract group common structures. Based on the group common structures of amyloid-beta (A beta) positive AD patients and A beta negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. Results: The proposed UMI demonstrates a more substantial statistical discrimination power to distinguish the longitudinal groups with different APOE epsilon 4 genotypes than the hippocampal volume measurements. And different APOE epsilon 4 allele load affects the shrinkage rate of the hippocampus, i.e., HM genotype will cause the largest atrophy rate, followed by HT, and the smallest is NC. Conclusion: The UMIs may capture the APOE epsilon 4 risk allele-induced brain morphometry abnormalities and reveal the dose effects of APOE epsilon 4 on the hippocampal morphology in cognitively normal individuals.