Alzheimer’s disease (AD) is a major neurodegenerative disorder causing memory loss and cognitive dementia affecting more than 4 million patients in US. The characteristic component of neuron cells of AD patients is extracellular senile plaque composed of amyloid ß (Aß) fibrils with generic cross-ß structure. Evidences have been accumulating that the main cytotoxic agent for AD is Aß oligomers.

We study Aß oligomers using molecular dynamics simulation. Replica exchange molecular dynamics is employed for exhaustive conformational sampling of Aß oligomer system, using united atom force field and implicit solvation model. Analysis of conformational ensembles shows that Aß dimers and tetramers exhibit shared globular conformations with elevated ß-strand content, which is sharply contrasted to Aß monomers. This study is expected to improve our understanding of Aß oligomer formation and toxicity with significant implications for drug design.