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Amyloid Diseases at the Molecular Level: General Overview and Focus on AL Amyloidosis

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Amyloid and Related Disorders

Part of the book series: Current Clinical Pathology ((CCPATH))

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Abstract

The amyloidoses encompass a heterogeneous group of diseases, wherein a misfolded protein accumulates extracellularly in the form of amyloid deposits, resulting in tissue damage and organ dysfunction.

Intrinsic instability, increased concentration, proteolytic cleavage and/or mutations of a precursor protein favour its conversion into an aggregation-prone misfolded state, which ultimately results in the formation of amyloid fibrils through poorly identified prefibrilllar oligomeric species. The latter are believed to be the main culprit for the toxicity.

Numerous unrelated proteins can undergo this process, resulting in different types of the disease. Among these, systemic immunoglobulin light chain (AL) amyloidosis is caused by a usually small and non-proliferating plasma cell clone, which resides in the bone marrow and secretes an amyloidogenic light chain into the circulation. Almost any organ can be the site of amyloid deposition, rendering AL a truly protean condition. The identification of a monoclonal component in a patient with histological evidence of amyloid disease is strongly suggestive, but not pathognomonic, of AL amyloidosis.

Correct typing requires a scrupulous and multidisciplinary approach and forms the basis for an etiological therapy. Standard therapies aim at eradicating the amyloidogenic precursor, but novel complementary therapeutic approaches are under intense scrutiny.

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Acknowledgments

Supported by Grant No. 9965 from the Associazione Italiana per la Ricerca sul Cancro Special Program Molecular Clinical Oncology, Fondazione Cariplo Nobel Project, Italian Ministry of University and Research (PRIN No. 2007AE8FX2_003 and 2007XY59ZJ_005); Ministry of Health (Ricerca Finalizzata Malattie Rare), “Istituto Superiore di Sanità” (526D/63). MN is partially supported by an investigator fellowship from Collegio Ghislieri, Pavia.

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  1. Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Biochemistry, University of Pavia, Piazzale Golgi, 2, Pavia, 27100, Italy

    Mario Nuvolone M.D., Giovanni Palladini M.D., Ph.D. & Giampaolo Merlini M.D.

  2. Istituto Universitario di Studi Superiori, Pavia, Italy

    Mario Nuvolone M.D.

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  1. Mario Nuvolone M.D.
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  1. Bldg#110, Rm#2242, Department of Pathology, Loyola University Medical Center, S. First Avenue 2160, Maywood, 60153, Illinois, USA

    Maria M. Picken MD, PhD, FASN

  2. , Department of Laboratory Medicine and Pa, Mayo Clinic, First Street SW 200, Rochester, 55905, USA

    Ahmet Dogan, M.D., Ph.D.

  3. , Department of Renal Pathology, Bostwick Laboratories, Lake Ellenor Dr. 8001, Orlando, 32809, Florida, USA

    Guillermo A. Herrera, M.D.

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Nuvolone, M., Palladini, G., Merlini, G. (2012). Amyloid Diseases at the Molecular Level: General Overview and Focus on AL Amyloidosis. In: Picken MD, PhD, FASN, M., Dogan, M.D., Ph.D., A., Herrera, M.D., G. (eds) Amyloid and Related Disorders. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-60761-389-3_2

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