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.
