Figure 4.

Macrophages degrade Aβ42 via an apoE isoform-dependent manner. Macrophages isolated from targeted replacement mice expressing human apoE2 (E2), apoE3 (E3), or apoE4 (E4) were incubated with PDAPP mouse brain sections for 48 or 96 h. Adjacent sections were incubated with media alone as control (Con). A, B, Aβ42 remaining in the sections (A) or released into the media (B) after incubation was measured by ELISA and plotted as a percentage of control value. n = 6 sections per treatment. Representative data from one experiment that was repeated three times with similar results. *p < 0.05, ***p < 0.001 versus control; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 versus E2 macrophages. C, The degradation of Aβ42 in PDAPP brain sections after incubation with E2, E3, or E4 macrophages for 96 h was verified by quantitative IP-MALDI analysis. n = 6 sections per treatment; ***p < 0.001 versus control; ^#p < 0.05, ^##p < 0.01 versus E2 macrophages. E2 or E4 macrophages were administered bilaterally (0.5 × 10⁶ cells) via intracerebral injection into the right or left cerebral cortices, respectively, of old heterozygous PDAPP mice (28 months). D, Three days after injection, brain Aβ was calculated as the difference between Aβ burden proximal to the injection site and the amount of Aβ remaining within the injection site. n = 7 animals. **p < 0.01 versus E2 injection sites. Representative data from one experiment that was repeated two times with similar results. Error bars represent the SE measurement.