To conclude, our work demonstrates that SEIRA spectroscopic combinations with membrane systems provide a valuable tool to explore the (mis)folding trajectories, with a specific focus on events occurring at/in the membrane mimicking a target interface during neurodegenerative diseases. Furthermore, the surface enhancement enables detecting species during early stages, involving oligomers relevant to Aβ-mediated toxicity. As such, we complement computational studies that explore similar events as well as experimental approaches that focus on larger aggregates in later stages of fibrilization, and provide a platform for in-situ testing of inhibitors with molecular structure information to support the search for new therapeutic strategies.