Well accepted as a molecule that plays an important role in the development of Alzheimer’s disease, the amyloid-beta (Aβ) molecule, an extracellular cleaved component of the amyloid precursor protein (APP), has been shown to form oligomers and penetrate neuronal cells to initiate the cascade of cell death. Exactly how these oligomers of Aβ enter the cell is not known. Several levels of molecular assembly have been known to take place, which includes binding to the cell membrane surface by the Aβ clusters. In an effort to more clearly define the specific parameters of the membrane that are favorable for the binding of Aβ and entry, we have used a special pair-wave heterodyning surface plasmon resonance apparatus that is sensitive to 50 fM of the protein in solution in a label-free environment. To mimic membrane surface, we used a nominally equimolar mixture of cholesterol, sphingomyelin and a fluid-phase phospholipid doped with 2% monosialoganglioside (33% POPC, 33% SM, 32% Chol, and 2% GM1), which mimics raft compositions of the plasma membrane. Data show that at concentrations lower than 500 nM, Aβ adsorbs onto the membrane surface with little evidence for membrane disruption for several hours. Holding the Aβ at that concentration and waiting for a time of 5 hours, however, leads to membrane damage clearly seen in the SPR signal. At higher concentration of solution Aβ, the rate of damage is correspondingly higher. Notably, using simply POPC as the membrane surface produced no damage even when concentration of Aβ is increased to 1 uM. Further significance of having the raft constituent (POPC, SM, Chol) vs. the necessity of the presence of membrane ganglioside GM1 is being currently examined. We are also investigating the effects as a function of Aβ degree of oligomerization.