However, 10-month-old female APOE4-TR mice, unlike 10-month-old female APOE3-TR mice, did not show an increased IgG staining, but an obviously weaker staining in the brain (Fig. 1a, b), especially in hippocampus (Fig. 1a-d), a brain region critical for learning and memory and vulnerable to be affected at early stages of AD [28]. Here, APOE is linked to Alzheimer disease.