Many types of Aβ oligomers, such as ADDLs, amylospheroids, paranuclei or hexameric Aβ42cc 9 have been prepared using these approaches. Soluble Aβ oligomers have been prepared incubating synthetic Aβ samples under specific conditions hypothesized to stabilize a given Aβ oligomer form (culture media, pH, T, salts, …) or engineering Aβ variants to lock the peptide in a conformation that is incompatible with fibril formation 9. Since the amounts of Aβ fibrillar plaques do not correlate with cognitive decline 8 researchers have focused on the study of both soluble and membrane-associated Aβ oligomers to identify the Aβ form responsible for neurotoxicity. Moreover, there is a less described pathway that considers that upon APP cleavage, a fraction of Aβ remains in the membrane evolving into membrane-associated Aβ oligomers, which would be directly responsible for compromising neuronal membrane integrity 7. Due to its hydrophobic nature, Aβ then aggregates into multiple species, commonly referred to as soluble Aβ oligomers, which eventually evolve into Aβ fibrils 3, 4, 5, 6, the main component of amyloid plaques. Upon APP cleavage, it is generally considered that Aβ is released to the extracellular environment. Aβ is obtained from a membrane protein, the amyloid precursor protein (APP), through the sequential cleavage of β- and γ-secretase 2. However, there is great controversy in establishing the exact Aβ form responsible for neurotoxicity. Substantial genetic evidence links the amyloid-β peptide (Aβ) to Alzheimer’s disease (AD) 1. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. Notably, Aβ(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimerʼs disease (AD).