LRP1 mediates Aβ uptake and degradation in primary astrocytes. A, Mouse primary astrocytes were transduced with lentiviral mediated control or LRP1 shRNA and were analyzed 48 h after transfection. Western blotting showed that LRP1 expression was significantly downregulated in primary astrocytes. **p < 0.01 (two-tailed Student's t test). B, Primary astrocytes with or without LRP1 knockdown were incubated with FAM-Aβ42 (500 nm) for 1 or 2 h at 37°C, and the cell-associated Aβ42 was analyzed by FACS. Representative results of five independent experiments performed in triplicate are shown. **p < 0.01 (two-way ANOVA). C, Primary astrocytes with or without LRP1 knockdown were incubated with FAM-Aβ42 (200 or 500 nm) for 2 h at 4°C and analyzed by FACS. Representative results from three independent experiments performed in triplicate are shown. D, Control and LRP1-KD astrocytes were allowed to internalize Aβ42 (1 μm) for 2 h at 37°C (gray bars); parallel cultures were washed and incubated for an additional 6 h in medium lacking Aβ42 (black bars) and analyzed by ELISA. *p < 0.05 (two-way ANOVA). **p < 0.01 (two-way ANOVA). E, The decrease of internalized Aβ is estimated as cellular clearance. Data are mean ± SD. *p < 0.05 (two-tailed Student's t test).