Probing the structure of toxic amyloid oligomers

Structural models of the toxic species involved in the development of Alzheimer's disease are of utmost importance to understand the molecular mechanism and to describe early biomarkers of the disease. Among toxic species, soluble oligomers of amyloid-beta peptides assembled into particles of less than 10 nm of diameter, are particularly important. These particles, differently from larger aggregates found in protein deposits, are responsible for spreading cell damages over brain regions, thus rapidly impairing brain functions. We report of recent contributions to monitor conformational organization due to environmental changes in this molecular system. By combining molecular models [1,2] and several spectroscopies (surface enhanced Raman spectroscopy, atomic force microscopy, and double electron-electron spin resonance) [3,4], we provided new insights into the specific arrangement of residues when the toxic state of peptides is achieved. These results point to possible early diagnosis of the disease, before late aggregation occurs.