Fluorescence anisotropy: A method for early detection of Alzheimer beta-peptide (A beta) aggregation

Time-resolved anisotropy measurements (TRAMS) have been used to study the a ggregation of the beta -amyloid (A beta) peptide which is suspected of play ing a central role in the pathogenesis of Alzheimer's Disease (AD), The exp eriments, which employ small quantities of fluorescently-labelled A beta, i n addition to the untagged peptide, have shown that the sensitive TRAMS tec hnique detects the presence of preformed "seed" particles in freshly prepar ed solutions of A beta, More importantly, as 100 muM solutions of A beta co ntaining tagged A beta at a concentration level of either 0.5 or 1 muM are incubated, the TRAMS prove capable of detection of the peptide aggregation process through the appearance of a continuously increasing "residual aniso tropy" within the time-resolved fluorescence data. The method detects A bet a aggregation in its earliest stages, well before complexation becomes appa rent in more conventional methods such as the thioflavin T fluorescence ass ay. The TRAMS approach promises to provide a most attractive route for esta blishment of a high-throughput procedure for the early detection of the pre sence of amyloid aggregates in the screening of biological samples, (C) 200 1 Academic Press.