Figure 1.

A schematic diagram illustrating the possible roles of secreted-frizzled-related protein 1 (SFRP1) in Alzheimer’s disease (AD). Astrocyte- and microglial (and other cell types)-secreted SFRP1 inhibit metalloproteinase domain-containing protein (ADAM10)-mediated non-amyloidogenic processing of amyloid precursor protein (APP). SFRP1 could also interfere with fibril/protofibril formation by amyloid β (Aβ), thus potentially preserving Aβ oligomers. SFRP1 also inhibits Wnt signaling, which is important for neuronal function and synaptic integrity. On the other hand, SFRP1 could be tumor suppressive via its inhibition of ADAM10’s sheddase activity, which liberates the ectodomain of growth/metastasis promoting proteins such as human epidermal growth factor receptor 2 (HER2) and the low affinity neurotrophin receptor (p75^NTR). See text for more details.