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

The progressive deposition of the amyloid beta peptide (A beta) in fibrillar 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 formation using a variety of assays and under different experimental conditions. We describe in detail the morphological development of the A beta polymerization process from pseudo-spherical structures and protofibrils to mature thioflavin-T-positive/Congo red-positive amyloid fibrils. Moreover, we structurally characterize the various polymorphic fibrillar assemblies using transmission electron microscopy and determine their mass using scanning transmission electron microscopy. These results provide the framework for future investigations into how target compounds may interfere with the polymerization process. Such substances might have a therapeutic potential in AD. (C) 2000 Academic Press.