The oligomers of the Amyloid beta peptide are strongly suspected to cause Alzheimers disease, but the underlying mechanism is unclear.It is known that as the peptide transits from the monomer to the oligomer, its membrane affinity increases by more than an order of magnitude (1).This may be a contributing factor in the toxicity of this extracellular peptide.Here we explore the structural basis of this increased affinity.We follow the evolution of the structure with aggregation by flash-freezing different intermediates, and interrogate their structure using vibrational, fluorescence and solid state NMR spectroscopies (1).We find that the early oligomers (n-mers with n＜10) have a structure which have a hairpin-like beta sheet rich structure much like the mature fibrils, with one major difference.The oligomers seem to have two anti-parallel beta sheet strands connected by a beta-turn, while the fibrils have a parallel beta sheet architecture with a non-beta hairpin tum.To investigate the structure in the membrane, we develop a Surface Enhanced Raman Spectroscopy (SERS) based technique which can determine the conformation of membrane-bound proteins, even at low micro Molar concentrations, and even in the presence of a substantial membrane-free fraction.Our results suggest a structure very similar to that observed in the solution.Interestingly, this would allow a "porin" like β-barrel structure, providing a structural basis for the membrane permeabilization hypothesis about the mechanism of Aβ oligomer toxicity.