Soluble amyloid precursor protein alpha (sAPPα) enhances proliferation in an EGF/bFGF-independent manner. (a) Neural progenitor cell (NPC)-conditioned media that has been immunodepleted of sAPP with 22C11 antibodies fails to recover GM6001-induced proliferation deficits of NPCs, as assayed by neurosphere diameter in a neurosphere formation assay. In contrast, NPC-conditioned media immunodepleted with control IgG antibodies successfully recovers NPC proliferation. (b) A neurosphere formation assay was performed without growth factors (EGF and bFGF), and NPCs were treated with an inactive inhibitor (NC), GM6001 (GM), or GM6001 + recombinant sAPPα (GM+rec sAPPα). The proliferative effect of sAPPα on GM6001-treated neurosphere (GM) in medium devoid of EGF/bFGF and the proliferative effect of EGF/bFGF on GM6001-treated neurospheres are greater than the effect of EGF/bFGF on neurospheres treated with NC, suggesting a synergistic effect of sAPPα and EGF/bFGF. Error bars represent standard error of the mean. *P < 0.01, analysis of variance with post hoc analysis. bFGF, basic fibroblast growth factor; EGF, epidermal growth factor.