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American Journal of Physiology. Heart... Feb 2012Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited... (Review)
Review
Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed "cardiac amyloidosis" or "amyloid cardiomyopathy." Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis.
Topics: Amyloidosis; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac
PubMed: 22058156
DOI: 10.1152/ajpheart.00815.2011 -
Biomolecules Sep 2017Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have... (Review)
Review
Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic species in amyloid assembly reactions, it is remarkable that cells can produce these functional amyloids without suffering any obvious ill effect. Although the precise mechanisms are unclear, there are a number of ways in which amyloid toxicity may be prevented. These include regulating the level of the amyloidogenic peptides and proteins, minimising the production of prefibrillar oligomers in amyloid assembly reactions, sequestrating amyloids within membrane bound organelles, controlling amyloid assembly by other molecules, and disassembling the fibrils under physiological conditions. Crucially, a better understanding of how toxicity is avoided in the production of functional amyloids may provide insights into the prevention of amyloid toxicity in amyloidoses.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Peptides
PubMed: 28937655
DOI: 10.3390/biom7040071 -
Journal of Clinical Pathology Feb 2005The cardiovascular system is a common target of amyloidosis. This review presents the current clinical and diagnostic approach to amyloidosis, with the emphasis on... (Review)
Review
The cardiovascular system is a common target of amyloidosis. This review presents the current clinical and diagnostic approach to amyloidosis, with the emphasis on cardiovascular involvement. It summarises recent nomenclature, classification, and pathogenesis of amyloidosis. In addition, non-invasive possibilities are discussed, together with endomyocardial biopsies in the diagnosis of cardiac amyloidosis. Finally, recent advances in treatment and prognostic implications are presented.
Topics: Aging; Algorithms; Amyloidosis; Cardiovascular Diseases; Diagnostic Errors; Heart Diseases; Humans; Immunohistochemistry; Microscopy, Electron; Myocardium; Prognosis
PubMed: 15677530
DOI: 10.1136/jcp.2004.017293 -
Upsala Journal of Medical Sciences May 2012Although AL amyloidosis usually is a systemic disease, strictly localized AL deposits are not exceptionally rare. Such case reports form a considerable body of published... (Review)
Review
Although AL amyloidosis usually is a systemic disease, strictly localized AL deposits are not exceptionally rare. Such case reports form a considerable body of published articles. Although both AL amyloidosis types are formed from an N-terminal segment of a monoclonal immunoglobulin light chain, a typical localized AL amyloid differs from the systemic counterpart by the morphological appearance of the amyloid, and presence of clonal plasma cells and of giant cells. In this article it is pointed out that localized AL amyloidosis ('amyloidoma') represents a true plasma cell neoplasm and not a pseudotumor. The pathogenesis of localized AL amyloidosis may differ from that of the systemic type, a suggestion underlined by the fact that localized AL amyloidosis of kappa type is as common as that of lambda origin, in contrast to the systemic form where lambda chains constitute the overwhelming majority of cases. It is suggested that oligomeric assemblies of the produced immunoglobulin light chain are toxic to plasma cells, which in this way commit suicide.
Topics: Amyloidosis; Humans; Neoplasms
PubMed: 22335280
DOI: 10.3109/03009734.2012.654861 -
The American Journal of Managed Care Jun 2017Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease characterized by deposition of amyloid fibrils in various organs and tissues of the body.... (Review)
Review
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease characterized by deposition of amyloid fibrils in various organs and tissues of the body. There are a wide variety of clinical presentations for this multisystemic disorder, so it is often misdiagnosed or subject to delayed diagnosis. Although the exact prevalence is difficult to determine, existing estimates suggest a worldwide prevalence of 50,000 individuals, with varying phenotypic presentations of disease. Due to the heterogeneous nature of its presentation, incorrect or delayed diagnosis can severely impact quality of life for these patients. hATTR amyloidosis can lead to significant disability and mortality. After an accurate diagnosis of hATTR amyloidosis is established, new patients should undergo appropriate therapy as soon as possible. Current treatment options for hATTR amyloidosis are limited, but orthotopic liver transplant serves as an established option for patients with early-stage disease. Consequently, there is a need for new, effective, and safe therapies.
Topics: Amyloidosis, Familial; Cost of Illness; Humans
PubMed: 28978215
DOI: No ID Found -
JNMA; Journal of the Nepal Medical... Oct 2023Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in...
UNLABELLED
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease.
KEYWORDS
cardiomyopathies; case reports; primary amyloidosis.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Bortezomib; Renal Insufficiency; Prognosis
PubMed: 38289775
DOI: 10.31729/jnma.8297 -
Molecules (Basel, Switzerland) Aug 2021Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or... (Review)
Review
Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrated the appearance of small globular oligomeric species during the incubation of amyloid beta peptide (Aβ). Nerve biopsy specimens from patients with systemic amyloidosis have suggested that globular structures similar to Aβ oligomers were generated from amorphous electron-dense materials and later developed into mature amyloid fibrils. Schwann cells adjacent to amyloid fibrils become atrophic and degenerative, suggesting that the direct tissue damage induced by amyloid fibrils plays an important role in systemic amyloidosis. In contrast, there is increasing evidence that oligomers, rather than amyloid fibrils, are responsible for cell death in neurodegenerative diseases, particularly Alzheimer's disease. Disease-modifying therapies based on the pathophysiology of amyloidosis have now become available. Aducanumab, a human monoclonal antibody against the aggregated form of Aβ, was recently approved for Alzheimer's disease, and other monoclonal antibodies, including gantenerumab, solanezumab, and lecanemab, could also be up for approval. As many other agents for amyloidosis will be developed in the future, studies to develop sensitive clinical scales for identifying improvement and markers that can act as surrogates for clinical scales should be conducted.
Topics: Amyloid; Amyloidosis; Animals; Humans; Organ Specificity; Protein Aggregates; Schwann Cells
PubMed: 34443678
DOI: 10.3390/molecules26165091 -
Thorax May 1999
Review
Topics: Amyloidosis; Humans; Respiratory System; Respiratory Tract Diseases
PubMed: 10212113
DOI: 10.1136/thx.54.5.444 -
PloS One 2018Since the late 1990s, high mortality and declining populations have been reported among sea birds including Herring gulls (Larus argentatus) from the Baltic Sea area in...
Since the late 1990s, high mortality and declining populations have been reported among sea birds including Herring gulls (Larus argentatus) from the Baltic Sea area in Northern Europe. Repeated BoNT type C/D botulism outbreaks have occurred, but it remains unclear whether this is the sole and primary cause of mortality. Thiamine deficiency has also been suggested as a causal or contributing factor. With this study, we aimed to investigate gross and microscopic pathology in Herring gulls from affected breeding sites in Sweden in search of contributing diseases. Herring gulls from Iceland served as controls. Necropsies and histopathology were performed on 75 birds, of which 12 showed signs of disease at the time of necropsy. Parasites of various classes and tissues were commonly observed independent of host age, e.g. oesophageal capillariosis and nematode infection in the proventriculus and gizzard with severe inflammation, air sac larid pentastomes and bursal trematodiasis in pre-fledglings. Gross and microscopic findings are described. Notably, amyloidosis was diagnosed in 93 and 33% of the adult birds from Sweden and Iceland, respectively (p<0.001), with more pronounced deposits in Swedish birds (p<0.001). Gastrointestinal deposits were observed in the walls of arteries or arterioles, and occasionally in villi near the mucosal surface. Amyloid was identified within the intestinal lumen in one severely affected gull suggesting the possibility of oral seeding and the existence of a primed state as previously described in some mammals and chickens. This could speculatively explain the high occurrence and previously reported rapid onset of amyloidosis upon inflammation or captivity in Herring gulls. Amyloid-induced malabsorbtion is also a possibility. The Herring gull SAA/AA protein sequence was shown to be highly conserved but differed at the N-terminus from other avian species.
Topics: Amino Acid Sequence; Amyloidosis; Animals; Avian Proteins; Bird Diseases; Bursa of Fabricius; Charadriiformes; Disease Outbreaks; Female; Gastrointestinal Tract; Male; Sequence Alignment; Sweden
PubMed: 29494674
DOI: 10.1371/journal.pone.0193265 -
Pathology Oncology Research : POR 2023Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant... (Review)
Review
Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
Topics: Male; Humans; Aged, 80 and over; Pneumothorax; Amyloidosis; Lung; Lung Diseases
PubMed: 37808084
DOI: 10.3389/pore.2023.1611390