In this study, we further determined that the alterations of IgG in the brain of 10-month-old female APOE4-TR mice were region-specific, with significant lower IgG levels in AD vulnerable areas like neocortex, entorhinal cortex and hippocampus, but not in AD relatively intact brain regions like thalamus and cerebellum, suggesting APOE4, together with ageing and sex, affecting IgG levels in certain brain regions. Here, APOE is linked to Alzheimer disease.