Early aggregation of amyloid-β(1–42) studied by fluorescence correlation spectroscopy

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting cognitive and memory abilities and is believed to be linked to the formation and accumulation of neurotoxic aggregates of the Amyloid-P peptide (Aj3). In particular, it is the formation of soluble pre-fibrillar oligomers within the early stage of Aj3 aggregation which is thought to representa key step in the development of AD, thus underlining the interest in characterizing the aggregation process and the nature of these aggregates. In this context, fluorescence correlation spectroscopy (FCS) has emerged as a valuable alternative for the study of these systems in solution. lndeed, the use ofFCS to study terminally labelled Aj3 provides a means to detect changes in the size and concentration of initially monomeric Aj3 samples by monitoring these fluorescently labelled species fi:eely diffusing in solution with single-molecule resolution. Herein, we show how to cmploy FCS to study the early aggregation process of AP(l-42) and how this can be used to estimate the critica! concentration for oligomer formation and to characterize the aggregates formed.