Studies on the in vitro assembly of A beta 1-40: Implications for the search for A beta fibril formation inhibitors

The progressive deposition of the amyloid beta peptide (A beta) in fibrilla r form is a key feature in the development of the pathology in Alzheimer's disease (AD). We have characterized the time course of A beta fibril format ion using a variety of assays and under different experimental conditions. We describe in detail the morphological development of the A beta polymeriz ation process from pseudo-spherical structures and protofibrils to mature t hioflavin-T-positive/Congo red-positive amyloid fibrils. Moreover, we struc turally characterize the various polymorphic fibrillar assemblies using tra nsmission electron microscopy and determine their mass using scanning trans mission electron microscopy. These results provide the framework for future investigations into how target compounds may interfere with the polymeriza tion process. Such substances might have a therapeutic potential in AD. (C) 2000 Academic Press.