FIGURE 4.

ApoE4 associated oxidative stress. Path A: The presence of APOE4 impairs the basal expression of antioxidant proteins such as SOD, HSP, TRX1 and COXIV and may impair ability to buffer oxidative challenge. Path B: ApoE4 exhibits a reduced affinity for reactive oxygen species and lipid peroxidation byproducts, likely due to a decreased number of ROS binding cysteine residues relative to that of ApoE2 and ApoE3. Combined, these pathways result in elevated ROS accumulation causing lipid peroxidation enhanced oxidative toxicity, ultimately increasing susceptibility to cell death. Abbreviations: ApoE4, apolipoprotein E4; COXIV, cytochrome oxidase subunit 4; HSP, heat shock protein; SOD, superoxide dismutase; TRX, thioredoxin; ROS, reactive oxygen species. Created with BioRender.com