Selenium and Episodic Memory: The Moderating Role of Apolipoprotein E ε4

Background: Selenium (Se), a vital trace element, plays a neuroprotective role by mitigating oxidative stress through selenoproteins and regulating metal balance. The apolipoprotein E ε4 allele (APOE4), a significant genetic risk factor for Alzheimer's disease (AD), has been linked to reduced Se levels and weakened antioxidant capacity. This research explores the association between serum Se concentrations and cognitive performance, with an emphasis on how APOE4 status influences this relationship. Methods: This study included 196 older adults from community and memory clinic settings, who underwent assessments for episodic memory, global cognition, and non-memory functions using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, with serum selenium levels analyzed via inductively coupled plasma-mass spectrometry (ICP-MS) and APOE genotyping conducted to determine allele status. Results: Higher serum Se levels were associated with better episodic memory score (EMS) (B = 0.065, 95% CI = 0.020-0.110, p = 0.005) and CERAD total score (TS) (B = 0.119, 95% CI = 0.046-0.193, p = 0.002). However, the interaction between Se and APOE4 status significantly affected EMS (B = -0.074, 95% CI = -0.109 to -0.039, p < 0.001), with significant benefits observed in APOE4-negative participants. Conclusions: This study highlights the genotype-specific impact of Se on cognitive health, emphasizing the need for personalized nutritional interventions targeting Se levels, particularly for APOE4-negative individuals. Future research should further elucidate the mechanisms of Se's effects and assess its therapeutic potential in aging populations.