FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 349:583-596 August 7, 2003 Number 6 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF PDA Full Text Purchase this article Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

The amyloidoses constitute a large group of diseases in which misfolding of extracellular protein has a prominent role. This dynamic process, which occurs in parallel with or as an alternative to physiologic folding, generates insoluble, toxic protein aggregates that are deposited in tissues in bundles of -sheet fibrillar protein (Figure 1). (A -sheet consists of strands of polypeptides in zigzag formation, as shown in Figure 2.) These amyloid deposits are identified on the basis of their apple-green birefringence under a polarized light microscope after staining with Congo red and the presence of rigid, nonbranching fibrils 7.5 to . . . [Full Text of this Article]

Molecular Mechanisms

Biochemical Characteristics of Amyloidogenic Proteins

A Dynamic View of the Pathogenic Process

Mutations and the Molecular Mechanism of Amyloid Formation

            Immunoglobulin Light Chains

            Familial Amyloidosis

            The Role of Instability

            Proteolysis

Amyloidosis as a Conformational Disease

Is Amyloidosis a Protein-Mediated Transmissible Disease?

The Common Constituents of Amyloid

Clinical Implications

Tissue Specificity of Amyloid Deposition

Mechanism of Tissue Damage

Diagnostic Problems and Pitfalls

Molecular Targets and Therapeutic Strategies

Effective Therapies

Future Perspectives

Source Information

From the Amyloid Center, Biotechnology Research Laboratory, University Hospital IRCCS Policlinico San Matteo; and the Department of Biochemistry, University of Pavia — both in Pavia, Italy.

Address reprint requests to Dr. Merlini at the Amyloid Center, Biotechnology Research Laboratory, Padiglione Forlanini, University Hospital IRCCS Policlinico San Matteo, Piazzale Golgi, 2, 27100 Pavia, Italy, or at gmerlini@smatteo.pv.it.

Related Letters:

Molecular Mechanisms of Amyloidosis
Sungur C. I., van der Hilst J. C.H., Simon A., Drenth J. P.H., Merlini G., Bellotti V.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:1872-1873, Nov 6, 2003. Correspondence

This article has been cited by other articles:

• van der Hilst, J. C. H., Yamada, T., Op den Camp, H. J. M., van der Meer, J. W. M., Drenth, J. P. H., Simon, A. (2008). Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1: potential explanation for higher risk of type AA amyloidosis. Rheumatology (Oxford) 47: 1651-1654 [Abstract] [Full Text]  
• Lavatelli, F., Perlman, D. H., Spencer, B., Prokaeva, T., McComb, M. E., Theberge, R., Connors, L. H., Bellotti, V., Seldin, D. C., Merlini, G., Skinner, M., Costello, C. E. (2008). Amyloidogenic and Associated Proteins in Systemic Amyloidosis Proteome of Adipose Tissue. Mol. Cell. Proteomics 7: 1570-1583 [Abstract] [Full Text]  
• Piccoli, G. B., Soragna, G., Palladini, G., Magnano, A., Sargiotto, A., Picciotto, G., Terzolo, M. (2008). End-stage renal failure due to amyloidosis and recurrent fever on dialysis--is there a link?. Nephrol Dial Transplant 23: 2419-2421 [Full Text]  
• Herczenik, E., Gebbink, M. F. B. G. (2008). Molecular and cellular aspects of protein misfolding and disease. FASEB J. 22: 2115-2133 [Abstract] [Full Text]  
• Yao, Q., Furst, D. E. (2008). Autoinflammatory diseases: an update of clinical and genetic aspects. Rheumatology (Oxford) 47: 946-951 [Abstract] [Full Text]  
• Lovell, M. A., Lynn, B. C., Xiong, S., Quinn, J. F., Kaye, J., Markesbery, W. R. (2008). An aberrant protein complex in CSF as a biomarker of Alzheimer disease. Neurology 70: 2212-2218 [Abstract] [Full Text]  
• Kingsbury, J. S., Laue, T. M., Klimtchuk, E. S., Theberge, R., Costello, C. E., Connors, L. H. (2008). The Modulation of Transthyretin Tetramer Stability by Cysteine 10 Adducts and the Drug Diflunisal: DIRECT ANALYSIS BY FLUORESCENCE-DETECTED ANALYTICAL ULTRACENTRIFUGATION. J. Biol. Chem. 283: 11887-11896 [Abstract] [Full Text]  
• Scalvini, T., Martini, P. R., Gambera, A., Tardanico, R., Biasi, L., Scolari, F., Gregorini, G., Agabiti Rosei, E. (2008). Spermatogenic and Steroidogenic Impairment of the Testicle Characterizes the Hereditary Leucine-75-Proline Apolipoprotein A-I Amyloidosis. J. Clin. Endocrinol. Metab. 93: 1850-1853 [Abstract] [Full Text]  
• van der Hilst, J. C. H., Kluve-Beckerman, B., Bodar, E. J., van der Meer, J. W. M., Drenth, J. P. H., Simon, A. (2008). Lovastatin inhibits formation of AA amyloid. J. Leukoc. Biol. 83: 1295-1299 [Abstract] [Full Text]  
• Bochtler, T., Hegenbart, U., Cremer, F. W., Heiss, C., Benner, A., Hose, D., Moos, M., Bila, J., Bartram, C. R., Ho, A. D., Goldschmidt, H., Jauch, A., Schonland, S. O. (2008). Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability. Blood 111: 4700-4705 [Abstract] [Full Text]  
• Mignot, A., Bridoux, F., Thierry, A., Varnous, S., Pujo, M., Delcourt, A., Gombert, J. M., Goujon, J.-M., Favreau, F., Touchard, G., Herpin, D., Jaccard, A. (2008). Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis. haematol 93: e32-e35 [Abstract] [Full Text]  
• Yilmaz, M. I., Sonmez, A., Saglam, M., Qureshi, A. R., Carrero, J. J., Caglar, K., Eyileten, T., Cakir, E., Oguz, Y., Vural, A., Yenicesu, M., Lindholm, B., Stenvinkel, P., Axelsson, J. (2008). ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction. J. Am. Soc. Nephrol. 19: 388-395 [Abstract] [Full Text]  
• Reixach, N., Foss, T. R., Santelli, E., Pascual, J., Kelly, J. W., Buxbaum, J. N. (2008). Human-Murine Transthyretin Heterotetramers Are Kinetically Stable and Non-amyloidogenic: A LESSON IN THE GENERATION OF TRANSGENIC MODELS OF DISEASES INVOLVING OLIGOMERIC PROTEINS. J. Biol. Chem. 283: 2098-2107 [Abstract] [Full Text]  
• Zhou, P., Teruya-Feldstein, J., Lu, P., Fleisher, M., Olshen, A., Comenzo, R. L (2008). Calreticulin expression in the clonal plasma cells of patients with systemic light-chain (AL-) amyloidosis is associated with response to high-dose melphalan. Blood 111: 549-557 [Abstract] [Full Text]  
• Selvanayagam, J. B., Hawkins, P. N., Paul, B., Myerson, S. G., Neubauer, S. (2007). Evaluation and Management of the Cardiac Amyloidosis. J Am Coll Cardiol 50: 2101-2110 [Abstract] [Full Text]  
• Feng, D., Edwards, W. D., Oh, J. K., Chandrasekaran, K., Grogan, M., Martinez, M. W., Syed, I. I., Hughes, D. A., Lust, J. A., Jaffe, A. S., Gertz, M. A., Klarich, K. W. (2007). Intracardiac Thrombosis and Embolism in Patients With Cardiac Amyloidosis. Circulation 116: 2420-2426 [Abstract] [Full Text]  
• Sanchorawala, V., Skinner, M., Quillen, K., Finn, K. T., Doros, G., Seldin, D. C. (2007). Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation. Blood 110: 3561-3563 [Abstract] [Full Text]  
• Sitia, R., Palladini, G., Merlini, G. (2007). Bortezomib in the treatment of AL amyloidosis: targeted therapy?. haematol 92: 1302-1307 [Full Text]  
• Kastritis, E., Anagnostopoulos, A., Roussou, M., Toumanidis, S., Pamboukas, C., Migkou, M., Tassidou, A., Xilouri, I., Delibasi, S., Psimenou, E., Mellou, S., Terpos, E., Nanas, J., Dimopoulos, M. A. (2007). Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. haematol 92: 1351-1358 [Abstract] [Full Text]  
• Yin, F.-Y., Chen, Y.-H., Yu, C.-M., Pon, Y.-C., Lee, H.-J. (2007). Kinetic Refolding Barrier of Guanidinium Chloride Denatured Goose {delta}-Crystallin Leads to Regular Aggregate Formation. Biophys. J 93: 1235-1245 [Abstract] [Full Text]  
• Dember, L. M., Hawkins, P. N., Hazenberg, B. P.C., Gorevic, P. D., Merlini, G., Butrimiene, I., Livneh, A., Lesnyak, O., Puechal, X., Lachmann, H. J., Obici, L., Balshaw, R., Garceau, D., Hauck, W., Skinner, M., the Eprodisate for AA Amyloidosis Trial Group, (2007). Eprodisate for the Treatment of Renal Disease in AA Amyloidosis. NEJM 356: 2349-2360 [Abstract] [Full Text]  
• Lachmann, H. J., Goodman, H. J.B., Gilbertson, J. A., Gallimore, J. R., Sabin, C. A., Gillmore, J. D., Hawkins, P. N. (2007). Natural History and Outcome in Systemic AA Amyloidosis. NEJM 356: 2361-2371 [Abstract] [Full Text]  
• Bergesio, F., Ciciani, A. M., Santostefano, M., Brugnano, R., Manganaro, M., Palladini, G., Palma, A. M. D., Gallo, M., Tosi, P. L., Salvadori, M., on behalf of the Immunopathology Group of the Ital, (2007). Renal involvement in systemic amyloidosis--an Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant 22: 1608-1618 [Abstract] [Full Text]  
• Hazenberg, B. P.C., van Rijswijk, M. H., Lub-de Hooge, M. N., Vellenga, E., Haagsma, E. B., Posthumus, M. D., Jager, P. L. (2007). Diagnostic Performance and Prognostic Value of Extravascular Retention of 123I-Labeled Serum Amyloid P Component in Systemic Amyloidosis. JNM 48: 865-872 [Abstract] [Full Text]  
• Leung, N., Dispenzieri, A., Lacy, M. Q., Kumar, S. K., Hayman, S. R., Fervenza, F. C., Cha, S. S., Gertz, M. A. (2007). Severity of Baseline Proteinuria Predicts Renal Response in Immunoglobulin Light Chain-Associated Amyloidosis after Autologous Stem Cell Transplantation. CJASN 2: 440-444 [Abstract] [Full Text]  
• Jacob, E. K., Edwards, W. D., Zucker, M., D'Cruz, C., Seshan, S. V., Crow, F. W., Highsmith, W. E. (2007). Homozygous Transthyretin Mutation in an African American Male. J. Mol. Diagn. 9: 127-131 [Abstract] [Full Text]  
• Dember, L. M. (2006). Amyloidosis-Associated Kidney Disease. J. Am. Soc. Nephrol. 17: 3458-3471 [Abstract] [Full Text]  
• Sanchorawala, V. (2006). Light-Chain (AL) Amyloidosis: Diagnosis and Treatment. CJASN 1: 1331-1341 [Abstract] [Full Text]  
• Merlini, G., Stone, M. J. (2006). Dangerous small B-cell clones. Blood 108: 2520-2530 [Abstract] [Full Text]  
• Shah, K. B., Inoue, Y., Mehra, M. R. (2006). Amyloidosis and the heart: a comprehensive review.. Arch Intern Med 166: 1805-1813 [Abstract] [Full Text]  
• Palladini, G., Lavatelli, F., Russo, P., Perlini, S., Perfetti, V., Bosoni, T., Obici, L., Bradwell, A. R., D'Eril, G. M., Fogari, R., Moratti, R., Merlini, G. (2006). Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 107: 3854-3858 [Abstract] [Full Text]  
• Comenzo, R. L., Zhou, P., Fleisher, M., Clark, B., Teruya-Feldstein, J. (2006). Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins. Blood 107: 3489-3491 [Abstract] [Full Text]  
• Dispenzieri, A., Lacy, M. Q., Katzmann, J. A., Rajkumar, S. V., Abraham, R. S., Hayman, S. R., Kumar, S. K., Clark, R., Kyle, R. A., Litzow, M. R., Inwards, D. J., Ansell, S. M., Micallef, I. M., Porrata, L. F., Elliott, M. A., Johnston, P. B., Greipp, P. R., Witzig, T. E., Zeldenrust, S. R., Russell, S. J., Gastineau, D., Gertz, M. A. (2006). Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 107: 3378-3383 [Abstract] [Full Text]  
• Yan, Y.-B., Zhang, J., He, H.-W., Zhou, H.-M. (2006). Oligomerization and Aggregation of Bovine Pancreatic Ribonuclease A: Characteristic Events Observed by FTIR Spectroscopy. Biophys. J 90: 2525-2533 [Abstract] [Full Text]  
• Rocken, C., Tautenhahn, J., Buhling, F., Sachwitz, D., Vockler, S., Goette, A., Burger, T. (2006). Prevalence and pathology of amyloid in atherosclerotic arteries.. Arterioscler. Thromb. Vasc. Bio. 26: 676-677 [Full Text]  
• Korenaga, T., Yan, J., Sawashita, J., Matsushita, T., Naiki, H., Hosokawa, M., Mori, M., Higuchi, K., Fu, X. (2006). Transmission of Amyloidosis in Offspring of Mice with AApoAII Amyloidosis. Am. J. Pathol. 168: 898-906 [Abstract] [Full Text]  
• Caccialanza, R., Palladini, G., Klersy, C., Cena, H., Vagia, C., Cameletti, B., Russo, P., Lavatelli, F., Merlini, G. (2006). Nutritional status of outpatients with systemic immunoglobulin light-chain amyloidosis 1. Am. J. Clin. Nutr. 83: 350-354 [Abstract] [Full Text]  
• Bosca, M M, Perez-Baylach, C M, Solis, M A, Anton, R, Mayordomo, E, Pons, S, Minguez, M, Benages, A (2006). Secondary amyloidosis in Crohn's disease: treatment with tumour necrosis factor inhibitor. Gut 55: 294-295 [Full Text]  
• Shivaprasad, S., Wetzel, R. (2006). Scanning Cysteine Mutagenesis Analysis of Abeta-(1-40) Amyloid Fibrils. J. Biol. Chem. 281: 993-1000 [Abstract] [Full Text]  
• Gregorini, G., Izzi, C., Obici, L., Tardanico, R., Rocken, C., Viola, B. F., Capistrano, M., Donadei, S., Biasi, L., Scalvini, T., Merlini, G., Scolari, F. (2005). Renal Apolipoprotein A-I Amyloidosis: A Rare and Usually Ignored Cause of Hereditary Tubulointerstitial Nephritis. J. Am. Soc. Nephrol. 16: 3680-3686 [Abstract] [Full Text]  
• Falk, R. H. (2005). Diagnosis and Management of the Cardiac Amyloidoses. Circulation 112: 2047-2060 [Full Text]  
• Perugini, E., Guidalotti, P. L., Salvi, F., Cooke, R. M.T., Pettinato, C., Riva, L., Leone, O., Farsad, M., Ciliberti, P., Bacchi-Reggiani, L., Fallani, F., Branzi, A., Rapezzi, C. (2005). Noninvasive Etiologic Diagnosis of Cardiac Amyloidosis Using 99mTc-3,3-Diphosphono-1,2-Propanodicarboxylic Acid Scintigraphy. J Am Coll Cardiol 46: 1076-1084 [Abstract] [Full Text]  
• Dember, L. M., Shepard, J.-A. O., Nesta, F., Stone, J. R. (2005). Case 15-2005 - An 80-Year-Old Man with Shortness of Breath, Edema, and Proteinuria. NEJM 352: 2111-2119 [Full Text]  
• Giorgetti, S., Rossi, A., Mangione, P., Raimondi, S., Marini, S., Stoppini, M., Corazza, A., Viglino, P., Esposito, G., Cetta, G., Merlini, G., Bellotti, V. (2005). {beta}2-Microglobulin isoforms display an heterogeneous affinity for type I collagen. Protein Sci. 14: 696-702 [Abstract] [Full Text]  
• Kholova, I, Niessen, H W M (2005). Amyloid in the cardiovascular system: a review. J. Clin. Pathol. 58: 125-133 [Abstract] [Full Text]  
• Kim, D. Y., Taylor, H. W., Eades, S. C., Cho, D.-Y. (2005). Systemic AL Amyloidosis Associated with Multiple Myeloma in a Horse. Vet Pathol 42: 81-84 [Abstract] [Full Text]  
• Trinkaus-Randall, V., Walsh, M. T., Steeves, S., Monis, G., Connors, L. H., Skinner, M. (2005). Cellular Response of Cardiac Fibroblasts to Amyloidogenic Light Chains. Am. J. Pathol. 166: 197-208 [Abstract] [Full Text]  
• Dhodapkar, M. V., Hussein, M. A., Rasmussen, E., Solomon, A., Larson, R. A., Crowley, J. J., Barlogie, B. (2004). Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood 104: 3520-3526 [Abstract] [Full Text]  
• CLEMENT, K., VIGUERIE, N., POITOU, C., CARETTE, C., PELLOUX, V., CURAT, C. A., SICARD, A., ROME, S., BENIS, A., ZUCKER, J.-D., VIDAL, H., LAVILLE, M., BARSH, G. S., BASDEVANT, A., STICH, V., CANCELLO, R., LANGIN, D. (2004). Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J. 18: 1657-1669 [Abstract] [Full Text]  
• Torricelli, C, Capurro, E, Santucci, A, Paffetti, A, D'Ambrosio, C, Scaloni, A, Maioli, E, Pacini, A (2004). Multiple plasma proteins control atrial natriuretic peptide (ANP) aggregation. J Mol Endocrinol 33: 335-341 [Abstract] [Full Text]  
• Brenner, D. A., Jain, M., Pimentel, D. R., Wang, B., Connors, L. H., Skinner, M., Apstein, C. S., Liao, R. (2004). Human Amyloidogenic Light Chains Directly Impair Cardiomyocyte Function Through an Increase in Cellular Oxidant Stress. Circ. Res. 94: 1008-1010 [Abstract] [Full Text]  
• Palladini, G., Perfetti, V., Obici, L., Caccialanza, R., Semino, A., Adami, F., Cavallero, G., Rustichelli, R., Virga, G., Merlini, G. (2004). Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 103: 2936-2938 [Abstract] [Full Text]  
• Corazza, A., Pettirossi, F., Viglino, P., Verdone, G., Garcia, J., Dumy, P., Giorgetti, S., Mangione, P., Raimondi, S., Stoppini, M., Bellotti, V., Esposito, G. (2004). Properties of Some Variants of Human {beta}2-Microglobulin and Amyloidogenesis. J. Biol. Chem. 279: 9176-9189 [Abstract] [Full Text]  
• Reixach, N., Deechongkit, S., Jiang, X., Kelly, J. W., Buxbaum, J. N. (2004). Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc. Natl. Acad. Sci. USA 101: 2817-2822 [Abstract] [Full Text]  
• Gertz, M. A., Merlini, G., Treon, S. P. (2004). Amyloidosis and Waldenstrom's Macroglobulinemia. ASH Education Book 2004: 257-282 [Abstract] [Full Text]  
• Sungur, C. I., van der Hilst, J. C.H., Simon, A., Drenth, J. P.H., Merlini, G., Bellotti, V. (2003). Molecular Mechanisms of Amyloidosis. NEJM 349: 1872-1873 [Full Text]