Association of ApoE Gene Polymorphisms With Circulating Biomarkers, Oxidative Stress, and Physiological Markers in Early- and Late-onset Depression in Older Adults: A Case-control Study

Background: Geriatric depression is a heterogeneous disorder influenced by genetic vulnerability, oxidative stress, and aging-related biological changes. Apolipoprotein E (ApoE), a key regulator of lipid metabolism and neuroinflammation, has been implicated in neuropsychiatric disorders, and its relationship with oxidative stress and age of onset of depression remains incompletely understood. Methods: A total of 230 participants were enrolled, including 39 early-onset depression (EOD) patients, 76 late-onset depression (LOD) patients, and 115 age- and sex-matched healthy controls. Oxidative stress markers were quantified spectrophotometrically. Serum ApoE levels were measured by enzyme-linked immunosorbent assay (ELISA) and ApoE genotyping (rs429358 and rs7412) was conducted using polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). Results: EOD and LOD groups exhibited significantly elevated lipid peroxidation (LPO) and glutathione reductase (GR) activity compared to controls ( p < .001). Superoxide dismutase (SOD) activity differed significantly across groups ( p = .022). Serum ApoE concentrations were significantly higher in depressed individuals, with higher levels observed in LOD ( p < .001). Although ApoE genotype distribution did not differ significantly among groups, allele-wise analysis revealed a higher frequency of the ε4 allele in depressed individuals ( p = .015). Participants carrying the ε4 allele showed significantly higher LPO levels ( p = .027). Conclusions: Geriatric depression is associated with increased oxidative damage and elevated circulatory ApoE levels. ApoE ε4 carriage is associated with increased oxidative stress, suggesting an association between genetic variation and oxidative stress in EOD and LOD.