-
Journal of the American College of... Nov 2019The prevalence of calcific aortic stenosis (AS) and of cardiac amyloidosis (CA) increases with age, and their association is not uncommon in the elderly. The... (Review)
Review
The prevalence of calcific aortic stenosis (AS) and of cardiac amyloidosis (CA) increases with age, and their association is not uncommon in the elderly. The identification of CA is particularly challenging in patients with AS because these 2 conditions share several features. It is estimated that ≤15% of the AS population and ≤30% of the subset with low-flow, low-gradient pattern may have CA. In patients with AS, CA is associated with increased risk of heart failure, mortality, and treatment futility with aortic valve replacement. In case of suspicion of CA, it is thus crucial to confirm the diagnosis to guide therapeutic management of AS and eventually implement recently developed pharmacological treatment dedicated to transthyretin amyloidosis. Given the high surgical risk of patients with AS and concomitant CA, transcatheter aortic valve replacement may be preferred to surgery in these patients.
Topics: Amyloidosis; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Humans; Prevalence
PubMed: 31753206
DOI: 10.1016/j.jacc.2019.09.056 -
Molecules (Basel, Switzerland) Feb 2022The amyloid hypothesis of Alzheimer's disease has long been the predominant theory, suggesting that Alzheimer's disease is caused by the accumulation of amyloid beta... (Review)
Review
The amyloid hypothesis of Alzheimer's disease has long been the predominant theory, suggesting that Alzheimer's disease is caused by the accumulation of amyloid beta protein (Aβ) in the brain, leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer's disease (AD). Currently, it is believed that altered biochemistry of the Aβ cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of Aβ in the brain.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloidosis; Animals; Autophagy; Biomarkers; Brain; Disease Management; Disease Susceptibility; Gene Expression Regulation; Humans; Plaque, Amyloid; Risk Factors
PubMed: 35209007
DOI: 10.3390/molecules27041210 -
Blood Cancer Journal May 2021Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing... (Review)
Review
Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage. Disease presentation is rather vague, and the hallmark of treatment is early diagnosis before irreversible end-organ damage. Once diagnosed, treatment decision is transplant-driven whereby ~20% of patients are eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction. In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment with the recent addition of daratumumab to the current emerging standard of care. In general, management of AL amyloidosis is aimed at achieving deep, durable responses with very close monitoring for early detection of relapse/refractory disease. This article provides a comprehensive review of the management of patients with AL amyloidosis including goals of therapy, current treatment guidelines in the setting of both ASCT-eligibility and ineligibility, treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease.
Topics: Animals; Antineoplastic Agents; Bortezomib; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous
PubMed: 34006856
DOI: 10.1038/s41408-021-00486-4 -
Brazilian Journal of Medical and... 2022Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical... (Review)
Review
Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Amyloidosis, Familial; Congo Red; Humans; Immunoglobulin Light Chains
PubMed: 36197414
DOI: 10.1590/1414-431X2022e12284 -
Archives of Pathology & Laboratory... Feb 2017-Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To... (Review)
Review
CONTEXT
-Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To date, 31 fibril proteins have been identified in humans, and it is now recommended that amyloidoses be named after these fibril proteins. Based on this classification scheme, the most common forms of amyloidosis include systemic AL (formerly primary), systemic AA (formerly secondary), systemic wild-type ATTR (formerly age-related or senile systemic), and systemic hereditary ATTR amyloidosis (formerly familial amyloid polyneuropathy). Three different clinicopathologic forms of amyloidosis can be seen in the lungs: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, and tracheobronchial amyloidosis.
OBJECTIVE
-To clarify the relationship between the fibril protein-based amyloidosis classification system and the clinicopathologic forms of pulmonary amyloidosis and to provide a useful guide for diagnosing these entities for the practicing pathologist.
DATA SOURCES
-This is a narrative review based on PubMed searches and the authors' own experiences.
CONCLUSIONS
-Diffuse alveolar-septal amyloidosis is usually caused by systemic AL amyloidosis, whereas nodular pulmonary amyloidosis and tracheobronchial amyloidosis usually represent localized AL amyloidosis. However, these generalized scenarios cannot always be applied to individual cases. Because the treatment options for amyloidosis are dependent on the fibril protein-based classifications and whether the process is systemic or localized, the workup of new clinically relevant cases should include amyloid subtyping (preferably with mass spectrometry-based proteomic analysis) and further clinical investigation.
Topics: Amyloidosis; Humans; Lung Diseases
PubMed: 28134587
DOI: 10.5858/arpa.2016-0102-RA -
European Respiratory Review : An... Sep 2017Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually... (Review)
Review
Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually death. Pulmonary amyloidosis may be localised or part of systemic amyloidosis.Pulmonary interstitial amyloidosis is symptomatic only if the amyloid deposits severely affect gas exchange alveolar structure, thus resulting in serious respiratory impairment. Localised parenchymal involvement may be present as nodular amyloidosis or as amyloid deposits associated with localised lymphomas. Finally, tracheobronchial amyloidosis, which is usually not associated with evident clonal proliferation, may result in airway stenosis.Because the treatment options for amyloidosis are dependent on the fibril protein type, the workup of all new cases should include accurate determination of the amyloid protein. Most cases are asymptomatic and need only a careful follow-up. Diffuse alveolar-septal amyloidosis is treated according to the underlying systemic amyloidosis. Nodular pulmonary amyloidosis is usually localised, conservative excision is usually curative and the long-term prognosis is excellent. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions or external beam radiation therapy.
Topics: Amyloidosis; Animals; Humans; Lung; Lung Diseases, Interstitial; Prognosis; Tomography, X-Ray Computed
PubMed: 28877975
DOI: 10.1183/16000617.0046-2017 -
Journal of Advanced Research Feb 2022Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The... (Review)
Review
INTRODUCTION
Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The accumulation and deposition of proteins result in toxicity and cause deleterious effects on affected individuals known as amyloidosis. There are about fifty different proteins and peptides involved in amyloidosis including neurodegenerative diseases and diseases affecting vital organs. Despite the strenuous effort to find a suitable treatment option for these amyloid disorders, very few compounds had made it to unsuccessful clinical trials. It has become a compelling challenge to understand and manage amyloidosis with the increased life expectancy and ageing population.
OBJECTIVE
While most of the currently available literature and knowledge base focus on the amyloid inhibitory mechanism as a treatment option, it is equally important to organize and understand amyloid disaggregation strategies. Disaggregation strategies are important and crucial as they are present innately functional in many living systems and dissolution of preformed amyloids may provide a direct benefit in many pathological conditions. In this review, we have compiled the known amyloid disaggregation mechanism, interactions, and possibilities of using disaggregases as a treatment option for amyloidosis.
METHODS
We have provided the structural details using protein-ligand docking models to visualize the interaction between these disaggregases with amyloid fibrils and their respective proposed amyloid disaggregation mechanisms.
RESULTS
After reviewing and comparing the different amyloid disaggregase systems and their proposed mechanisms, we presented two different hypotheses for ATP independent disaggregases using L-PGDS as a model.
CONCLUSION
Finally, we have highlighted the importance of understanding the underlying disaggregation mechanisms used by these chaperones and organic compounds before the implementation of these disaggregases as a potential treatment option for amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Molecular Chaperones; Protein Aggregates
PubMed: 35127169
DOI: 10.1016/j.jare.2021.05.007 -
Journal of the National Comprehensive... Jan 2023Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index... (Review)
Review
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; In Situ Hybridization, Fluorescence; Plasma Cells; Risk Assessment
PubMed: 36630897
DOI: 10.6004/jnccn.2022.7077 -
Chronic Respiratory Disease 2006Amyloidosis is a disorder of protein folding in which normally soluble plasma proteins aggregate in an abnormal fibrillar form causing progressive disruption to tissue... (Review)
Review
Amyloidosis is a disorder of protein folding in which normally soluble plasma proteins aggregate in an abnormal fibrillar form causing progressive disruption to tissue structure and organ function. This review covers systemic AA and AL amyloidosis which may arise as a consequence of chronic respiratory conditions; the manifestations of both systemic and of localised amyloid deposition within the respiratory tract and provides a summary of current approaches to diagnosis and management.
Topics: Amyloidosis; Humans; Lung; Lung Diseases; Radiography
PubMed: 17190124
DOI: 10.1177/1479972306070066 -
Current Hematologic Malignancy Reports Aug 2021Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many... (Review)
Review
PURPOSE OF REVIEW
Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available.
RECENT FINDINGS
New imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating clinicians, a diagnostic algorithm for patients with suspected amyloidosis with or without cardiomyopathy is shown to help classify disease and to direct appropriate genetic testing and management. For patients with light chain disease, recently introduced treatments adopted from multiple myeloma therapies have significantly extended progression-free and overall survival as well as organ response. In addition, new medical interventions are now available for those with transthyretin amyloidosis. Although cardiac amyloidosis contributes significantly to the morbidity and mortality associated with systemic disease, new tools are available to assist with diagnosis, prognosis, and management.
Topics: Amyloidosis; Cardiomyopathies; Humans
PubMed: 34106429
DOI: 10.1007/s11899-021-00626-4