Amyloidogenic processing of APP was enhanced in APPsw-N2a cells cultured with microglia-conditioned media (MCM) from Mn-treated BV2 cells. (A–D) Western blot results on the expression levels of APP cleavage enzymes, BACE1, ADAM10, and PS1 in APPsw-N2a cells under different conditions. MCM, especially MCM from Mn-treated BV2 cells, significantly increased the levels of BACE1 (B) and PS1 (D). MCM from Mn-treated BV2 cells also significantly decreased the level of ADAM10 (C) in APPsw-N2a cells. (E–H) Western blot results on the expression levels of APP, C99, and C83 in APPsw-N2a cells. β-actin was used as an internal control. APP and C99 levels were increased in APPsw-N2a cells cultured with MCM from Mn-treated BV2 cells compared with vehicle, Mn alone, MCM alone groups (F,G). C83 levels were decreased in APPsw-N2a cells cultured with MCM from Mn-treated BV2 cells compared with the other three groups (H). (I,J) Enzyme-linked immunosorbent assay (ELISA) data showing that Mn, MCM, especially MCM from Mn-treated BV2 cells increased Aβ1–42 secretion (I) and decreased Aβ1–40 production (J) in APPsw-N2a cells. *p < 0.05, **p < 0.01, ***p < 0.001, two-way ANOVA, n = 5 for each group.