The ability to form stable cross‐β fibrils is an intrinsic physicochemical characteristic of the human β‐amyloid peptide (Aβ), which forms the brain amyloid of Alzheimer's disease (AD). The high amyloidogenicity and low solubility of this hydrophobic =40‐mer have been barriers to its study in the past, but the availability of synthetic peptide and new physical methods has enabled many novel approaches in recent years. Model systems for Aβ aggregation (relevant to initial nidus formation) and Aβ deposition (relevant to plaque growth and maturation! in vitro have allowed structure/activity relationships and kinetics to be explored quantitatively, and established that these processes' are biochemically distinct. Different forms of the peptide, with different physicochemical characteristics, are found in vascular and parenchymal amyloid. Various spectroscopic methods have been used to explore the three‐dimensional conformation of Aβ both in solution and in solid phase, and demonstrated that the peptide adopts a different configuration in each state. A significant conformational transition is essential to the transformation of Aβ from solution to fibril. These observations suggest new therapeutic targets for the t
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