Ultrastructural Arguments for the Extracellular Location of Amyloid Deposits


Amyloidosis is a disease characterized by deposition and accumulation of insoluble proteins as small or large deposits of a fibrillar material. Despite the fact that these deposits are ultrastructurally identical, the basic proteins are chemically different, so far being recognized over 25 amyloidogenic precursors [1]. All these proteins can be immuno-histochemically identified, thus leading to a more and more precise diagnosis and an appropriate treatment.
Amyloid fibrils have an 8 to 12 nm diameter, are extremely strong, highly ordered and organized and can be formed, as already mentioned, by a large number of proteins and peptides [2]. They are rigid, nonbranching, hollow-cored tubules randomly arranged. Examined in X-ray diffraction they have a characteristic ?-pleated sheet configuration. This macromolecular helix of 100 nm periodicity, formed by two twisted ?-pleated sheet micelles is responsible for the resistance of amyloid to solubilization or proteolytic digestion. The amyloid precursor peptides may be normal serum proteins, or abnormal degradation variants, which can be repetitively incorporated into a developing amyloid fibril. The P component of amyloid fibril is a pentagonal, 8 nm diameters, doughnut like glyco-protein, similar to complement component C1t and C-reactive protein. P component is probably the cause of amyloid deposit staining with iodine. All amyloids contain a proteoglycans matrix. Pure amyloid contains amyloid fibrils, P component and proteoglycans matrix. In tissue, the deposits are contaminated with varying amounts of plasma proteins and collagen. Variations in staining and density of amyloid result from different amounts of non-amyloid components attached to the fibrilar scaffold.