- [Alzheimer's disease]. [Journal Article]
- ZNZh Nevrol Psikhiatr Im S S Korsakova 2018; 118(1):77-81
- Alzheimer's disease (AD) is a serious medical and social problem of our time, while remaining the most common cause of dementia in the elderly. The leading symptom in the clinical picture of the dise...
Alzheimer's disease (AD) is a serious medical and social problem of our time, while remaining the most common cause of dementia in the elderly. The leading symptom in the clinical picture of the disease is a progressive loss of memory with further development of behavioral disorders. In the early stages of AD, patients are mostly managed by neurologists and differential diagnosis is carried out with a variety of neurodegenerative diseases. The authors present clinical criteria of AD diagnosis and consider diagnostic possibilities in the predementia stage using biological markers. With this purpose, modern concepts of the etiology and pathogenesis of AD and genetic aspects of pathology are considered. Contribution of many environmental factors to the initiation and progression of the disease process is evaluated. Mechanisms of cerebral amyloidosis and its characteristic neurological manifestations are considered.
- Molecular subtypes of Alzheimer's disease. [Journal Article]
- SRSci Rep 2018 Feb 19; 8(1):3269
- Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the bra...
Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.
- Animal models of monoclonal immunoglobulin-related renal diseases. [Review]
- NRNat Rev Nephrol 2018 Feb 19
- The renal deposition of monoclonal immunoglobulins can cause severe renal complications in patients with B cell and plasma cell lymphoproliferative disorders. The overproduction of a structurally uni...
The renal deposition of monoclonal immunoglobulins can cause severe renal complications in patients with B cell and plasma cell lymphoproliferative disorders. The overproduction of a structurally unique immunoglobulin can contribute to the abnormal propensity of monoclonal immunoglobulins to aggregate and deposit in specific organs. A wide range of renal diseases can occur in multiple myeloma or monoclonal gammopathy of renal significance, including tubular and glomerular disorders with organized or unorganized immunoglobulin deposits. The development of reliable experimental models is challenging owing to the inherent variability of immunoglobulins and the heterogeneity of the pathologies they produce. However, although imperfect, animal models are invaluable tools to understand the molecular pathogenesis of these diseases, and advances in creating genetically modified animals might provide novel approaches to evaluate innovative therapeutic interventions. We discuss the strategies employed to reproduce human monoclonal immunoglobulin-induced kidney lesions in animal models, and we highlight their advantages and shortcomings. We also discuss how these models have affected the management of these deposition diseases and might do so in the future. Finally, we discuss hypotheses that explain some limitations of the various models, and how these models might improve our understanding of other nephropathies without immunoglobulin involvement that have similar pathogenic mechanisms.
- Importance of renal biopsy in patients aged 60 years and older: Experience from a tertiary care hospital. [Journal Article]
- SJSaudi J Kidney Dis Transpl 2018 Jan-Feb; 29(1):140-144
- As the life expectancy is increasing, there is a rise in elderly population and consequent increase in the patients with renal disease. There is an inconsistency between clinical and histopathologica...
As the life expectancy is increasing, there is a rise in elderly population and consequent increase in the patients with renal disease. There is an inconsistency between clinical and histopathological diagnosis in elderly, and so renal biopsy is important in these patients to decide appropriate clinical management and prognosis. This study outlines the importance of renal biopsy in elderly and describes the clinical and pathologic spectrum of renal diseases in patient ≥60 years. All patients (age ≥60 years) undergoing renal biopsies from January 2011 to December 2014 were included in this retrospective study. The clinical presentation and biochemical findings were recorded, and the patients were grouped based on their clinical presentation. Renal biopsies were also evaluated. The mean age of patients was 67.7 ± 6.4 years with a male:female ratio of 3:1. The most common clinical manifestation was nephrotic syndrome (37.4%) followed by rapidly progressive renal failure (RPRF) (20.6%). Amyloidosis and membranous nephropathy were two most common diagnoses in patients with nephrotic presentation whereas pauci-immune crescentic glomerulonephritis and cast nephropathy were common in patients presenting with RPRF. Clinical diagnosis differed from the histopathological diagnosis in 32% cases of nephrotic syndrome. There was good agreement between clinical diagnosis and histology in cases with RPRF. In 73% cases of elderly with (Type II) diabetes suspected of having nondiabetic renal disease clinically, renal biopsy showed evidence of diabetic nephropathy. Renal biopsy is essential in the diagnosis of renal diseases even in elderly. Amyloidosis and membranous nephropathy are common causes of nephrotic syndrome in elderly. Renal biopsy is very useful in diagnosing cast nephropathy and amyloidosis as they are not suspected clinically. It is also helpful in elderly diabetics without retinopathy to differentiate between diabetic and nondiabetic kidney diseases.
- Newly designed 11-gene panel reveals first case of hereditary amyloidosis captured by massive parallel sequencing. [Journal Article]
- JCJ Clin Pathol 2018 Feb 17
- CONCLUSIONS: We report one positive case of hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy of unknown significance and set up first panel for NGS in hereditary amyloidosis. This work may facilitate successful implementation of the NGS method by other researchers or clinicians and may improve the diagnostic process after validation.
- Daratumumab resistance is frequent in advanced stage multiple myeloma patients irrespectively of CD38 expression, and is related to dismal prognosis. [Journal Article]
- EJEur J Haematol 2018 Feb 17
- CONCLUSIONS: Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short lived, stressing the administration of this agent should be early in the course of the disease. This article is protected by copyright. All rights reserved.
- Boundaries between familial Mediterranean fever and juvenile spondyloarthritis: Analysis of three French retrospective cohorts. [Journal Article]
- JBJoint Bone Spine 2018 Feb 13
- CONCLUSIONS: Familial Mediterranean fever may be associated with typical pattern of juvenile spondyloarthritis. These patients, with less response to colchicine, should be diagnosed earlier and treated as for jSpA.
- Recurrent fever and arthralgia as the presentation of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Chinese girl: a case report and review of the literature. [Review]
- CRClin Rheumatol 2018 Feb 15
- Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is characterized by recurrent episodes of inflammation with fever, abdominal pain, chest pain, rash, myalgia, arthralgia, conjuncti...
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is characterized by recurrent episodes of inflammation with fever, abdominal pain, chest pain, rash, myalgia, arthralgia, conjunctivitis, and periorbital edema. This condition is a rare autosomal dominant disease that is strongly associated with heterozygous mutations in the tumor necrosis factor (TNF) receptor super family 1A (TNFRSF1A) gene. This condition is believed to be more common in Western countries than in Asian countries, and the AA amyloidosis rate for European countries is estimated to be 10%. Herein, we report the case of a 14-year-old girl with recurrent fever and arthralgia with inflammatory marker elevation for 10 years. After extensive investigation of the infectious etiology with negative results and similar phenomenon observed within her family, the diagnosis of TRAPS was made based on next-generation sequencing, which revealed a T50M mutation; she was also sensitive to corticosteroids. Although none of our TRAPS patients developed AA amyloidosis, we suggest the continual monitoring of urinalysis results and serum amyloid A concentrations during long-term follow-up. Moreover, we also reviewed the related literature and found no Asian patients who had developed AA amyloidosis.
- Canakinumab treatment in children with familial Mediterranean fever: report from a single center. [Journal Article]
- RIRheumatol Int 2018 Feb 15
- Familial Mediterranean fever (FMF), the most common hereditary autoinflammatory disorder is characterized by recurrent episodes of fever, serositis, arthritis. The major long-term result is amyloidos...
Familial Mediterranean fever (FMF), the most common hereditary autoinflammatory disorder is characterized by recurrent episodes of fever, serositis, arthritis. The major long-term result is amyloidosis. Colchicine remains the principle of the treatment; it not only prevents the acute attacks but also prevents the long-term complications such as amyloidosis; 5-10% of the patients are unresponsive to treatment. Recently new therapeutic options as anti-interleukin 1 agents are successfully used for the patients who do not respond to colchicine treatment. In this study, we retrospectively evaluated 11 pediatric colchicine-resistant FMF patients who were treated with canakinumab. Three of the patients had amyloidosis and two had uveitis. Based on our results, we suggest that canakinumab may be a safe and effective therapy in patients who are resistant to colchicine and even in the patients with amyloidosis. We also suggest that canakinumab might be a safe option for the patients with uveitis.
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- Serum Transthyretin: Predictor of Amyloidosis Outcomes? [Editorial]
- CHCirc Heart Fail 2018; 11(2):e004802