APOE genotype determines brain APOE protein levels during aging. (A) A representative Western blot analysis of homogenates prepared from APOE2, APOE3 and APOE4 mice hemibrains probed with anti-human APOE monoclonal antibody (HJ15.3). β-actin is shown as a loading control. (B) Quantification of APOE band intensity at 6, 12 and 18 months of age normalized to β-actin. Data are expressed as the mean ± SEM normalized to APOE3 at each age. n(6 months) = 12 APOE2, 10 APOE3, 12 APOE4; n(12 months) = 17 APOE2, 14 APOE3, 15 APOE4; n(18 months) = 10 each genotype; throughout data from individual male mice are graphed with a blue circle and from female with a red square. Post-hoc t-tests at 12 months of age: APOE2 = 142.6 ± 13.0 % of APOE3; t(29) = 3.279, p = 0.0027; APOE3 vs. APOE4 not significantly different (p = 0.066); and APOE2 = 183.0 ± 17.1 % of APOE4 t(30) = 4.835, p < 0.0001. At 18 months of age, APOE2 = 126.5 ± 5.7 % of APOE3; t(18) = 4.662, p = 0.0002); APOE3 = 117.1 ± 7.1 % of APOE4; t(18) = 2.405, p = 0.027; and APOE2 = 148.6 ± 8.4 % of APOE4 t(18) = 5.803, p = 0.0001. Throughout: *p < 0.05, **p < 0.01, ***p < 0.001. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)