Developing Topics.

Abstract

The HFE gene involves regulation of iron metabolism that directly participates in white matter (WM) myelination and neuroinflammations processes, while ApoE4 mutation are known to affect normal myelination through disruptions of iron and lipid metabolisms. Taken together, it is important to investigate the collective effects of HFE and the ApoE4 mutations, focusing on iron metabolism and neuronal inflammation during AD WM degeneration. Diffusion tensor imaging (DTI) MRI, cognitive and CSF biomarkers (sTREM2, Tau, Abete42) data were collected from ADNI database in the AD cohorts of ApoE4 carriers with and without HFEH63D polymorphism. Multivariate analysis with AMOS in SPSS software was used to establish and validate directed correlations using structural equation models (SEM).[1] RESULT: Prominent WM degeneration in AD is significantly attenuated in HFEH63D carriers (Fig.1). The negative and indirect correlation between HFEH63D genotype and CDR-cog (Fig. 2) suggests a protective role by HFEH63D mutation on WM degeneration and cognitive decline in AD ApoE4 carriers. As indicated by the negative and direct correlation between sTREM2 and CDR-cog, such a protective role during AD aging is likely due to the reduced neuroinflammation in the HFE polymorphism cohorts. Unified multivariate analysis with SEM allowed us to establish directed/causative relationships between genotyping and AD neurodegeneration-to-cognitive-decline within the ATN framework. Our SEM analysis demonstrated that the protective role in ADApoE4 carriers may involve in attenuated neuroinflammation by the altered iron management by HFEH63D polymorphism. Ref. [1]. Bagozzi, R. and Yi, Y. (1988) On the Evaluation of Structural Equation Models. Journal of the Academy of Marketing Sciences, 16, 74-94. https://doi.org/10.1007/BF02723327.