Tsuranobu Shirahama

The ultrastructural organization of the fibrous component of amyloid has been analyzed by means of high resolution electron microscopy of negatively stained isolated amyloid fibrils and of positively stained amyloid fibrils in thin tissue sections. It was found that a number of subunits could be resolved according to their dimensions. The following structural organization is proposed. The amyloid fibril, the fibrous component of amyloid as seen in electron microscopy of thin tissue sections, consists of a number of filaments aggregated side-by-side. These amyloid filaments are approximately 75-80 A in diameter and consist of five (or less likely six) subunits (amyloid protofibrils) which are arranged parallel to each other, longitudinal or slightly oblique to the long axis of the filament. The filament has often seemed to disperse into several longitudinal rows. The amyloid protofibril is about 25-35 A wide and appears to consist of two or three subunit strands helically arranged with a 35-50-A repeat (or, less likely, is composed of globular subunits aggregated end-to-end). These amyloid subprotofibrillar strands measure approximately 10-15 A in diameter.

Colchicine was found to have a strong inhibitory effect on amyloid induction in an animal model. When CBA/J mice were treated with colchicine concurrently with the amyloid induction regimen, the incidence of amyloidosis was, depending upon the dosage of colchicine, significantly decreased (0.005-0.010 mg colchicine per day) or completely blocked (more than 0.015 mg colchicine per day). The colchicine treatment was effective not only when colchicine was given for the entire course of the amyloid induction regimen but also when it was given only in the late pre-amyloid or the amyloid phase of the regimen or to the recipients after the transfer of amyloid. The data suggest the colchicine is effective in blocking amyloidogenesis at its final stage(s), while it may not affect significantly amyloid already deposited in the tissue.