Attr

Transthyretin

Systemic Localized

Prototypic familial amyloid polyneuropathy

Senile cardiac amyloidosis

Aß precursor

Localized

Alzheimers; ageing

APrP

Prion protein

Localized

Prion associated disorders

ACys

Cystatin C

Localized

Icelandic amyloid angiopathy

AFib

Fibrinogen Aa chain

Systemic

Hereditary, renal

Aß2M

ß-2 microglobulin

Systemic

Chronic hemodialysis

AApoA1

Apolipoprotein AI

Systemic

Liver, kidney, heart

AApoAII

Apolipoprotein AII

Systemic

Liver, kidney, heart

A Lys

Lysozyme

Systemic

Kidney, liver, spleen

A Gel

Gelsolin

Systemic

Finnish hereditary amyloidosis

AIAPP Islet-associated peptide Localized Amyloid of the islets; Type II diabetes

AIAPP Islet-associated peptide Localized Amyloid of the islets; Type II diabetes predominantly in defined target organs: 3-2 microglobulin in the joints, fibrinogen Aa in the kidney, and the transthyretin Met30 variant in the peripheral nerves.17 In AL amyloid, virtually every organ may be involved, most commonly the heart, kidneys, nerves, and liver. Importantly, the pattern of organ involvement may differ greatly between patients and seems to determine outcome. The reasons behind differences in organ tro-pism in different patients is not clear, but may be due to properties of the light chains themselves, or to their interactions with specific tissue glycosaminoglycans or cell-surface receptors, such as the receptor for advanced glycation end products (RAGE).18

An equally important, but poorly understood aspect of this disease is the mechanism by which the deposited amyloid fibrils cause tissue damage or organ dysfunction. For example, amyloid deposition in the heart due to either light chain or transthyretin-related amyloid leads to different clinical outcomes.19 Several possible explanations for the mechanism of tissue injury have been put forth. These include interactions with RAGE receptors,18 inflammatory response due to fibrillar intermediates, or direct cytoxicity of oligomeric precursors.20 Several clinical clues suggest that some of these mechanisms may be operative in AL amyloid as well. For example, significant improvement in organ function may occur after chemotherapy has halted the production of amyloidogenic light chains, but before the expected resolution of the amyloid deposits in the involved tissues.1121 Improved understanding of the mechanism of amyloid-associated tissue injury may allow novel approaches to preserve organ function and prolong survival in these patients.

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