APOE genotype is associated with Ex vivo inflammatory responses in healthy individuals: Potential implications for Alzheimer's disease

Background Apolipoprotein E ( APOE ) genotype and inflammation are each linked to Alzheimer’s disease (AD) risk. The APOE-ε4 ( APOE4 ) allele is associated with increased AD risk, while the APOE-ε2 ( APOE2 ) allele is protective. The mechanisms behind these associations remain unclear, particularly regarding the role of inflammation. This study examined the association between APOE genotype and different measures of inflammation, including mitogen-stimulated cytokine production ( ex vivo ) which provides a stable measure of immune response traits. Methods We examined basal and lipopolysaccharide (LPS)-stimulated cytokine levels (interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF)) and C-reactive protein (CRP) in blood samples from 91 healthy individuals (ages 18–51) of varying APOE genotypes . Results APOE4 carriers exhibited higher LPS-stimulated inflammatory responses (IL-1β, TNF-α) in peripheral whole blood compared to non-carriers, while APOE2 carriers showed a hypo-inflammatory profile (lower stimulated IL-1β) compared to APOE3 individuals. Conclusion Distinct inflammatory phenotypes were associated with APOE genotypes, with APOE4 carriers exhibiting a hyper-inflammatory response and APOE2 carriers exhibiting a hypo-inflammatory response. These profiles may contribute to differential AD risk, highlighting the potential involvement of inflammation in APOE -associated AD susceptibility.