Calprotectin influences the aggregation of metal-free and metal-bound amyloid- β by direct interaction

Proteins from the S100 family perform numerous functions and may contribute to Alzheimer's disease (AD). Herein, we report the effects of S100A8/S100A9 heterooligomer calprotectin (CP) and the S100B homodimer on metal-free and metal-bound amyloid- (A; A(40) and A(42)) aggregation in vitro. Studies performed with CP-Ser [S100A8(C42S)/S100A9(C3S) oligomer] indicate that the protein influences the aggregation profile for A(40) in both the absence and presence of metal ions [i.e., Zn(ii) and Cu(ii)]. Moreover, the detection of A(40)-CP-Ser complexes by mass spectrometry suggests a direct interaction as a possible mechanism for the involvement of CP in A(40) aggregation. Although the interaction of CP-Ser with A(40) impacts A(40) aggregation in vitro, the protein does not attenuate A-induced toxicity in SH-SY5Y cells. In contrast, S100B has a slight effect on the aggregation of A. Overall, this work supports a potential association of CP with A in the absence and presence of metal ions in AD.