An Historical Overview of the Amyloidoses

Abstract

The amyloidoses are a heterogenous group of clinical disorders that share the common finding of the abnormal deposition of insoluble proteins into various organs, with the result that these proteinaceous deposits disrupt cellular function and impair the integrity of the organs involved. Most typically, the abnormal protein deposition is the consequence of abnormal three dimensional folding of the culprit protein. The abnormal folding of the protein, in turn, may be due to a germ line mutation, may be due to an acquired mutation, or may be due to a polymorphism or characteristic of a normal protein that leads to abnormal folding, precipitation, and deposition of the protein, particularly when that protein is expressed at unusually high levels for a prolonged period of time. The clinical manifestations of an amyloid disorder are the consequences of the array of organs involved, the extent of amyloid deposition, and co-morbid conditions present in the individual patient. The array of organs involved, and the extent of organ involvement, in turn, depend in large part on the specific protein that is responsible for the amyloid deposition, and the process driving that protein’s production. In this chapter, a chronological overview is intended to summarize the critical insights into the patho-biology of amyloid accumulation of various types. These insights have allowed an improved understanding over time of the of the major subgroups and disease entities of the amyloidoses, leading to some degree of improvement in diagnosis and treatment outcomes. Unfortunately, as of this writing, treatment outcomes still remain poor for a large fraction of patients, and there is need for improvement in all aspects of the evaluation and management of these diseases.