The misfolding and aggregation of amyloid β (1-42) peptide is crucial for a mechanical understanding of the formation of Alzheimer's disease. To investigate the detailed aggregation pathway and mechanism, it is important to identify the secondary structures of different aggregation forms. Here, we report probing different amyloid β aggregations in real time by using correlated approaches such as shell-isolated surface-enhanced Raman spectroscopy, thioflavin T fluorescence assay, and atomic force microscopy imaging. Our experimental results of Raman shifts have been further demonstrated by theoretical calculation, which indicates that the Raman spectral fingerprint changes are originated from the amyloid β secondary structure changes. Copyright © 2013 John Wiley & Sons, Ltd.