Amyloidosis

Definition a group of diseases characterized by the deposition of an extracellular protein that has specific properties 

A fibrillary protein that varies with each disease 

Rank Cause of Death Number of Deaths Percentage 

Rank Cause of Death Percent of Total Deaths 

Oncogene Tumor Gene product Mechanism of Activation 

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Amyloidosis Occurs by the Deposition of Fragments of Various Plasma Proteins in Tissues... 

Brown, P., Goldfarb, L.G. and Gajdusek, D.C. (1991b). The new biology of spongiform encephalopathy infectious amyloidosis with a genetic twist. Lancet 337, 1019-1022. 

Nephrotic syndrome, multiple myeloma, Wilson s disease, and amyloidosis... 

Infiltrative myocardial diseases (e.g., amyloidosis, sarcoidosis, endomyocardial fibrosis)... 

Glomerular diseases (e.g., anti-glomerular basement membrane disease, focal segmental glomerularsclerosis, IgA nephropathy, hemolytic uremic syndrome, systemic lupus erythematosus, Alport s syndrome, amyloidosis, membranous nephropathy, and Goodpasture s syndrome)... 

Other diseases Autoimmune diseases Amyloidosis Aplastic anemia Paroxysmal nocturnal hemoglobinuria Fanconi s anemia Thalassemia major Sickle cell anemia Severe combined immunodeficiency Inborn errors of metabolism... 

Low level activation of MPS Interleukin-I Amyloidosis Hyperplastic liver foci Altered stem cell kinetics Altered drug metabolism Altered response to drugs C Biotechnics For biotechnics (and specifically monoclonal antibodies), factors affecting safety include... 

Table 3 Amyloidoses Recognized by the WHO International Nomenclature Committee on Amyloidosis... 

Plasma cell disorders Plasma cell disorders Inflammation-associated, familial Mediterranean fever Familial amyloidotic neuropathy, systemic senile amyloidosis Dialysis-associated amyloidosis Familial amyloidotic neuropathy, aortic amyloidosis Familial systemic amyloidosis Familial systemic amyloidosis Familial systemic amyloidosis Familial cerebral hemorrhage with amyloidosis Sporadic and familial Alzheimer s disease, familial cerebral hemorrhage with amyloidosis Spongiform encephalopathies C-cell thyroid tumors Insulinoma, type II diabetes Atrial amyloidosis Prolactinomas pituitary amyloidosis Iatrogenic amyloidosis Corneal amyloidosis ... 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

Helms LR, Wetzel R. Specificity of abnormal assembly in immunoglobulin light chain deposition disease and amyloidosis. J Mol Biol 1996 ... 

Kisilevsky R, Lemieux LJ, Fraser PE, Kong X, Hultin PG, Szarek WA. Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates implications for Alzheimer s disease. Nat Med 1995 1 143-148. 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

The neuromuscular compartment of the bowel wall is also affected in certain types of the Ehler-Danlos syndrome [162], maybe in amyloidosis [163], and in the presence of diffuse lymphocytic infiltration [164],... 

Diagnostic indications for nerve biopsy have become less frequent with improvements in EMG and nerve conduction techniques and the advent of specific molecular and biochemical tests for many inherited and acquired neuropathies. However, nerve biopsy does remain useful for diagnosis of vasculitis and amyloidosis, and plays an important role in research. 

Rajkumar, S. V., Gertz, M. A. and Kyle, R. A. Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am. J. Med. 104 232-237, 1998. 

Transgenic strategies have been used to create models of A (3 amyloidosis 785... 

BACE2 cleavages, which occur in non-neural tissues, preclude the formation of Ap peptides and thus are thought to protect these organs from Ap amyloidosis [43],... 

Second, we described the successful outcomes of Ap immunotherapy in mutant mice with Ap amyloidosis. Unfortunately, in humans, although Phase 1 trials with Ap peptide and adjuvant vaccination were not associated with any adverse events, Phase 2 trials were suspended because of severe adverse reactions (meningoencephalitis) in a subset of patients [79,90]. The pathology in a single case, consistent with T-cell meningitis [90], was interpreted to show some clearance of Ap deposits, yet these regions... 

Ghiso, J. and Wisniewski, T. An animal model of vascular amyloidosis. Nature Neurosci. 7 902-904, 2004. 

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