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Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. These diseases are a subset of a growing group of disorders attributed to misfolding of proteins. Among these are Alzheimer's disease and other neurodegenerative diseases; transmissible prion diseases; and genetic diseases caused by mutations that lead to misfolding, aggregation, and protein loss of function, such as certain of the cystic fibrosis mutations. Amyloid fibrils share a common β-pleated sheet structural conformation that confers unique staining properties. The term amyloid was coined by the pathologist Rudolf Virchow around 1854, who thought such deposits were cellulose-like under the microscope.
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Amyloid diseases are defined by the biochemical nature of the protein in the fibril deposits and are classified according to whether they are systemic or localized, acquired or inherited, and by their clinical patterns (Table 18-1). The accepted nomenclature is AX, where A indicates amyloidosis and X represents the protein in the fibril. AL is amyloid composed of immunoglobulin light chains (LCs) and has been called primary systemic amyloidosis; it arises from a clonal B cell disorder and may be associated with myeloma or lymphoma. AF groups the familial amyloidoses, most commonly due to mutations in transthyretin, the transport protein for thyroid hormone and retinol-binding protein. AA amyloid is composed of the acute-phase reactant serum amyloid A protein, occurs in the setting of chronic inflammatory or infectious diseases, and has been termed secondary amyloidosis. Aβ2M is amyloid composed of β2-microglobulin and occurs in individuals with end-stage renal disease (ESRD) of long duration. Aβ is the most common form of localized amyloidosis. Aβ is deposited in the brain in Alzheimer's disease and is derived from abnormal proteolytic processing of the amyloid precursor protein (APP).
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