Amyloidosis has lately emerged from the backwaters of pathological curiosity into the mainstream of clinical science. This has principally arisen following characterisation of the cerebral β-protein amyloid deposits that are a pathological hallmark and very likely the cause of Alzheimer’s disease. For scientists, as well as the British population at large, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease, and their association with prion protein amyloid have provided additional food for thought. At the same time much progress has been made in our understanding of systemic amyloidosis, which has revolutionised the clinical management and outcome of many affected patients.

Amyloid deposits consist mainly of amyloid fibrils.1 A prerequisite for developing amyloidosis is the sustained supply of an amyloid fibril precursor protein—that is, one which can undergo ‘off-pathway’ folding into an abnormal conformation that facilitates its incorporation into fibrillar aggregates. In many situations the fibril precursors are produced in abnormal abundance or with abnormal primary structure, or both. Many such proteins can form amyloid fibrils in vitro, their amino acid sequence appearing to determine their amyloidogenicity, but little is known about the factors that govern the anatomical distribution of the deposits or their clinical effects, and why certain forms of amyloid are deposited in some people but not in others. Despite the heterogeneity of their respective precursor proteins, the structure and biochemical properties of all amyloid fibrils are remarkably similar, including relative resistance to proteolysis. The fibrils associate in vivo with certain glycosaminoglycans and also with the normal plasma protein serum amyloid P component (SAP)² via a specific calcium dependent ligand binding interaction. The latter is the basis for our development of radiolabelled SAP as a diagnostic nuclear medicine tracer. Amyloid deposits probably exert much of their pathological effects directly through their physical presence, although this may not necessarily explain how they …