Soluble state high resolution atomic force microscopy study of Alzheimer's beta-amyloid oligomers.

We report here the direct observation of high resolution structures of assemblies of Alzheimer beta-amyloid oligomers and monomers using liquid atomic force microscopy (AFM). Visualization of nanoscale features of Abeta oligomers (also known as ADDLs) was carried out in tapping mode AFM in F12 solution. Our results indicate that ADDL preparations exist in solution primarily as a mixture of monomeric peptides and higher molecular mass oligomers. Our study clearly reveals that the size and shape of these oligomer aggregates exhibit a pronounced dependence on concentration. These studies show that wet AFM enables direct assessment of oligomers in physiological fluids and suggests that this method may be developed to visualize Abeta oligomers from human fluids.