The invention relates to the field of biochemistry, biophysical chemistry, molecular biology, structural biology and medicine. More in particular, the invention relates to cross-.beta. structure conformation. The invention provides a method for determining a difference in the cross-.beta. structure content of a protein in a reference sample compared to said protein in a test sample wherein the test sample has been subjected to a treatment that is expected to have an effect on the cross-.beta. structure content of said protein comprising--determining in said reference sample the cross-.beta. structure content of said protein--subjecting said protein to a treatment that is expected to have an effect on the cross-.beta. structure content to obtain said test sample--determining in said obtained test sample the cross-.beta. structure content of said protein--determining whether the cross-.beta. structure content of the reference sample is different from the cross-.beta. structure content in the test sample.