Interaction between Oligomers of Stefin B and Amyloid-β in Vitro and in Cells

To contribute to the question of the putative role of cystatins in Alzheimer disease and in neuroprotection in general, we studied the interaction between human stefin B (cystatin B) and amyloid-beta-(1-40) peptide (A beta). Using surface plasmon resonance and electrospray mass spectrometry we were able to show a direct interaction between the two proteins. As an interesting new fact, we show that stefin B binding to A beta is oligomer specific. The dimers and tetramers of stefin B, which bind A beta, are domain-swapped as judged from structural studies. Consistent with the binding results, the same oligomers of stefin B inhibit A beta fibril formation. When expressed in cultured cells, stefin B co-localizes with A beta intracellular inclusions. It also co-immunoprecipitates with the APP fragment containing the A beta epitope. Thus, stefin B is another APP/A beta-binding protein in vitro and likely in cells.