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

Time-resolved anisotropy measurements (TRAMS) have been used to study the aggregation of the beta -amyloid (A beta) peptide which is suspected of playing a central role in the pathogenesis of Alzheimer's Disease (AD), The experiments, which employ small quantities of fluorescently-labelled A beta, in addition to the untagged peptide, have shown that the sensitive TRAMS technique detects the presence of preformed "seed" particles in freshly prepared solutions of A beta, More importantly, as 100 muM solutions of A beta containing 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 anisotropy" within the time-resolved fluorescence data. The method detects A beta aggregation in its earliest stages, well before complexation becomes apparent in more conventional methods such as the thioflavin T fluorescence assay. The TRAMS approach promises to provide a most attractive route for establishment of a high-throughput procedure for the early detection of the presence of amyloid aggregates in the screening of biological samples, (C) 2001 Academic Press.