In vitro amyloid Aβ1-42 peptide aggregation monitoring by asymmetrical flow field-flow fractionation with multi-angle light scattering detection

Self-assembly of the 42-amino-acid-long amyloid peptide A beta(1-42) into insoluble fibrillar deposits in the brain is a crucial event in the pathogenesis of Alzheimer's disease. The fibril deposition occurs through an aggregation process during which transient and metastable oligomeric intermediates are intrinsically difficult to be accurately monitored and characterised. In this work, the time-dependent A beta(1-42) aggregation pattern is studied by asymmetrical flow field-flow fractionation with on-line multi-angle light scattering detection. This technique allows separating and obtaining information on the molar mass (M (r)) and size distribution of both the early-forming soluble aggregates and the late prefibrillar and fibrillar species, the latter having very high M (r). Preliminary results demonstrate that unique information on the dynamic aggregation process can be obtained, namely on the M (r) and size of the forming aggregates as well as on their formation kinetics.