INTERACTION BETWEEN APOEɛ4 AND HMGB1 IS ASSOCIATED WITH CORTICAL THINNING IN MILD COGNITIVE IMPAIRMENT INDIVIDUALS

Abstract

The presence of the apolipoprotein E4 (APOE4) allele, neuroinflammation, and cortical thinning have been shown to have an effect on disease progression from MCI to AD. However, the effect of interaction between APOE4, neuroinflammation and cortical thinning on subjects with MCI and dementia is unclear. We investigated the interaction between APOE4 and neuroinflammation as measured by high mobility group box 1 protein (HMGB1) plasma on cortical thinning in MCI compared to controls. 52 subjects were recruited; 25 MCI and 27 controls. Clinical information, genetic status, neuroinflammatory markers, and neuroimaging assessments were collected. FreeSurfer 6.0 was performed to study cortical thinning. Age, gender, and education were controlled as confounders. We also examined interaction effect between APOE4 status and neuroinflammatory markers in affecting regional cortical thickness. Multiple comparisons were corrected using a family wise error (FWE) cluster-based correction using Monte Carlo simulations with 10 000 iterations applied to the smoothed cortical thickness maps. Threshold for significance level was set at P < 0.001. The mean age of MCI subjects was 66.4 years and 40.7% were carrying at least 1 APOE4 allele. (Table 1). Plasma HMGB1 levels were significantly higher among MCI. Markers of systemic inflammation were comparable between the MCI and controls. APOE4 status was associated with cortical thinning in the frontal and insula regions among subjects with MCI. No association between APOE4 status and cortical thinning was found in controls. HMGB1 plasma levels were associated with cortical thinning in the frontal and temporal cortices in controls. Among MCI, HMGB1 levels were associated with cortical thinning in the frontal and insula cortices. Interaction effect between APOE4 status and HMGB1 plasma in MCI showed a more extensive pattern of cortical thinning in the frontal, temporal, and insula cortices (Fig. 1). HMGB1 was also significantly correlated with MMSE, MoCA, and episodic memory. Individually, APOE4 status and plasma HMGB1 are associated with reduction in cortical thickness in specific regions. The interaction between APOE4 and HMGB1 result in a more widespread pattern of cortical thinning. This suggestion that neuroinflammation having more pronounced impact among APOE4 positive MCI subjects will need to be duplicated in larger studies.