Disrupted Brain Structural Connectivity: Pathological Interactions Between Genetic APOE ε4 Status and Developed MCI Condition

The epsilon 4 allele of the apolipoprotein E (APOE) gene and mild cognitive impairment (MCI) are both risk factors for Alzheimer's disease (AD). One factor is genetic, and the other is a developed condition during the aging process. The current study intended to discover the interactions of these two factors, which may be useful in the construction of a sensitive biomarker for early identification and intervention. Eight hundred eighty-five Chinese Han ethnic subjects (aged 55 and older) completed neuropsychological tests and APOE genotyping. One hundred ten of these participants underwent magnetic resonance imaging (MRI) for T1 structural and diffusion tensor imaging scans. Subjects were divided into four groups according to APOE epsilon 4 carrying status and MCI condition: epsilon 4+ MCI, epsilon 4+ normal cognition (NC), epsilon 4- MCI, and epsilon 4- NC. In the studied Han population in Beijing, 16.9 % (epsilon 2 epsilon 4 = 1.1 %, epsilon 3 epsilon 4 = 14.8 %, and epsilon 4 epsilon 4 = 0.9 %) carried at least one epsilon 4 allele. Significant interactions between APOE epsilon 4 and MCI were found in general cognitive function (p = 0.001) and white matter connectivity network (clustering coefficient, p = 0.004, and local efficiency, p = 0.011); the combination of epsilon 4 positivity and MCI was accompanied by reductions in Mini-Mental Status Examination (MMSE) scores, global white matter network connectivity, and the right hippocampus (rHIP) nodal efficiency within that network (false discovery rate (FDR), p < 0.05). Our results suggest the presence of a genetic risk and MCI led to more severe pathological symptoms and could be informative in the implementation of clinical trials for early stages of AD.