Senile systemic amyloidosis

Transthyretin is a 147-residue transporter protein that is deposited as amyloid in senile systemic amyloidosis and familial amyloid polyneuropathy (Benson and Uemichi, 1996 Saraiva, 1995 Westermark et al., 1990). The protein s native structure is a 55-kDa dimer of dimers, or homotetramer, composed mainly of /1-sheets (Blake et al., 1978). The native monomer-to-monomer interface is formed by mutual, antiparallel extension of each monomer s two sheets (Fig. 7A) both four-stranded sheets in the monomers (DAGH and GBEF) become eight-stranded sheets in the dimer (DAGHH G A D and CBEFF E B C ) (Blake et al, 1978). In vitro at low... 

Westermark, P., Sletten, K.,Johansson, B., and Cornwell, G. G., Ill (1990). Fibril in senile systemic amyloidosis is derived from norma] transthyretin. Proc. Natl. Acad. Sci. USA 87, 2843-2845. 

Alzheimer s Disease Spongiform encephalopathies Primary systemic amyloidosis Secondary systemic amyloidosis Familial amyloidotic polyneuropathy I Senile systemic amyloidosis Hereditary cerebral amyloid angiopathy Haemodialysis-related amyloidosis Familial amyloidotic polyneuropahy II Finnish hereditary amyloidosis Type n diabetes... 

Most TTR variants are associated with extracellular deposition of amyloid fibrils in various tissue. These autosomal dominant hereditary amyloidoses include amyloidotic cardiomyopathy, familial amyloidotic polyneuropathy, and senile systemic amyloidosis. There is phenotypic variability (e.g., variable age of onset), suggesting that other factors may influence pathogenesis of the diseases. 

Senile systemic amyloidosis, cardiac involvement Spongiform encephalopathies... 

An instractive example of the effect of cysteine modification on amyloid formation is provided by the TTR protein. This plasma protein is a tetramer in solution, with four identical 127 amino acid sub-units and is responsible for transport of thyroxine and the retinol-binding protein-vitamin A complex (Hamilton and Benson 2001). Deposition of wtTTR occurs in senile systemic amyloidosis (SSA) (Table 1). This is a non-hereditary disorder that affects roughly 25% of individuals over the age of 80. The amyloid fibrils formed consist mainly of wfTTR and its fragments, and they build up in the heart. 

Ueda M, Ando Y, Haraoka K, et al. Aging and transthyretin-related amyloidosis pathologic examinations in pulmonary amyloidosis. Amyloid 2006 13(1) 24—30. Ng B, Connors LH, Davidoff R, et al. Senile systemic amyloidosis presenting with heart failure a comparison with light chain-associated amyloidosis. Arch Intern... 

Kunze WP. Senile pulmonary amyloidosis. Pathol Res Pract 1979 164(4) 413-422. Pitkanen P, Westermark P, Cornwell GG, III. Senile systemic amyloidosis. Am J Pathol 1984 117(3) 391-399. 

Westermark P, Bergstrom J, Solomon A, et al. Transthyretin-derived senile systemic amyloidosis clinicopathologic and structural considerations. Amyloid 2003 10 (suppl l) 48-54. 

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 ... 

Senile seminal vesicle amyloidosis Chronic inflammatory diseases, secondary systemic amyloidosis... 

Bergstrom J, Murphy C, Eulitz M, Weiss DT, Westermark GT, Solomon A, Westermark P (2001) Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis. Biochem Biephys Res Commun 285 903—908... 

Westermark, P., Pitkanan, P., Benson, L., Bahlquist, A., Olofsson, B. O., and Cornwell, G. G. (1985). Serum prealbumin and retinol-binding protein in the prealbumin-related senile and familial forms of systemic amyloidosis. Lab. Invest 52,314- 318. 

Senile systemic or age-related amyloidosis (SSA) results from the misfolding of wild-type transthyretin protein. Age-related amyloidosis occurs in systemic and localized (isolated atrial amyloid, senile aortic amyloidosis) forms. Elderly men are almost uniformly involved. Ng et al. (49) recently reported 18 SSA patients ranging in age from 67 to 86 years. 

Kyle RA, Spittell PC, Gertz MA, Li CY, Edwards WD, Olson LJ, Thibodeau SN. The premortem recognition of systemic senile amyloidosis with cardiac involvement. Am J Med 1996 101 395-400. 

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