APOE Genotype Alters Immunoglobulin Subtypes in Knock-In Mice

Abstract

Apolipoprotein E (APOE) alleles are strongly related to the risk of Alzheimer’s disease (AD). APOE genotype also affects inflammatory processes in response to damage. We tested whether APOE genotype affected the levels of specific immunoglobulins in healthy, uninfected APOE knock-in mice. We measured specific immunoglobulins in brain, spleen, and plasma. Levels of total IgG in brain and spleen were highest in APOE-ɛ3 mice, significantly higher than in APOE-ɛ2 and APOE-ɛ4 mice; no differences were observed for levels of total IgG in plasma. We also measured specific subtypes of IgG. IgG1 was only detectable in plasma and did not differ by APOE genotype. IgG3 was detectable in plasma and spleen, and also did not differ by APOE genotype. IgG2b showed the same pattern as levels of total IgG by APOE genotype, with the highest levels of IgG2b in brain, spleen, and plasma of APOE-ɛ3 mice. IgG2a showed an entirely different pattern, with significantly higher levels in spleen and plasma of APOE-ɛ4 mice compared to APOE-ɛ2 and APOE-ɛ3 mice. We also measured IgM and IgA in spleens and plasma of these mice. In spleen, APOE-ɛ4 mice had the lowest IgA levels and the highest levels of IgM; both being significantly different from APOE-ɛ2 mice. In total, murine IgG2a and IgM were highest in APOE-ɛ4 mice, while total IgG and Ig2b were highest in APOE-ɛ3 mice. These dramatically different distributions of immunoglobulins could allow for human AD risk biomarkers based on specific immunoglobulin subtypes.