Jonathan S. Harrison

By Jonathan S. Harrison, Yossi Cohen, Irina Ioffe and Shlomo Bulvik

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.

Part of the book: Amyloidosis

By Gilad A. Muth, Jonathan S. Harrison and Rohan Arora

Amyloid deposition plays a significant, albeit overlooked, role in neurologic disorders. Deposition of amyloid proteins in both the central and peripheral nervous systems lead to debilitating, and often deadly, organ dysfunction, including cerebral amyloid angiopathy, familial amyloid neuropathy, and Alzheimer’s disease (AD). Alzheimer’s disease is discussed in some detail in a separate chapter within this book, and therefore will not be discussed in detail in this chapter. In this chapter, we present the pathological mechanisms, disease manifestations, diagnostic approach, and treatment modalities for diseases of the nervous system caused by amyloid deposition. While significant strides have been made over the years in identifying key underlying pathologic mechanisms, the medical community’s understanding of these rare conditions remain limited. The primary goal of this chapter is to provide additional resources and information for clinicians to help identify these disorders early in their course before they cause irreparable damage to their patients.

Part of the book: Amyloidosis