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Neurology 2022 May 18. Epub 2022 May 18.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Objective: This study investigated the cutaneous small fiber pathology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and its clinical significance, i.e. the NOTCH3 deposition in cutaneous vasculatures and CNS neurodegeneration focusing on cognitive impairment. Read More

Front Neurosci 2022 27;16:837390. Epub 2022 Apr 27.

Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Amyloid beta (Aβ) is one of the proteins which aggregate in AD, and its key role in the disease pathogenesis is highlighted in the amyloid cascade hypothesis, which states that the deposition of Aβ in the brain parenchyma is a crucial initiating step in the future development of AD. The sensitivity of instruments used to measure proteins in blood and cerebrospinal fluid has significantly improved, such that Aβ can now successfully be measured in plasma. Read More

Ann Noninvasive Electrocardiol 2022 May 14:e12967. Epub 2022 May 14.

Department of Cardiology, National University Heart Centre, Singapore, Singapore.

Background: Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. Read More

Kidney Int Rep 2022 Apr 26;7(4):776-785. Epub 2022 Jan 26.

Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.

Introduction: Primary IgA nephropathy (IgAN) with light chain λ restriction in the mesangial deposits (IgAN-λ) has unique immunofluorescence (IF) features. Nevertheless, its clinicopathology and prognosis are still ambiguous.

Methods: From January 2002 to December 2020, the clinical and pathologic data of 3872 patients who were diagnosed with having primary IgAN by renal biopsy in our hospital were reviewed. Read More

J Alzheimers Dis 2022 Apr 25. Epub 2022 Apr 25.

The Framingham Heart Study, Framingham, MA, USA.

Background: Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer's disease (AD) and may offer utility for predicting preclinical disease.

Objective: To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals.

Methods: Plasma p-tau181 levels were measured at baseline in 52 [48% women, mean 64. Read More

Heart Fail Rev 2022 Apr 26. Epub 2022 Apr 26.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Cardiac involvement in amyloidosis is characterized by the extracellular deposition of misfolded proteins in the heart with the pathognomonic histological property of green birefringence when viewed under cross-polarized light after staining with Congo red. Although considered a rare disease, recent data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. The prognosis for transthyretin (TTR) amyloidosis (ATTR) amyloidosis is better than that for amyloid light-chain amyloidosis; however, it is not as good as for other etiologies heart failure. Read More

J Assoc Physicians India 2022 Apr;70(4):11-12

Sms Medical College and Hospital, Jaipur.

Multiple myeloma (MM) is a hematologic malignancy, characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. Patients presents with signs and symptoms related to the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains. Renal involvement with various presentations may be the first manifestation of the disease. Read More

Am J Hematol 2022 Jun 25;97(6):818-829. Epub 2022 Apr 25.

Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.

Disease Overview: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)."

Diagnosis: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Read More

Clin Nucl Med 2022 Apr 5. Epub 2022 Apr 5.

From the Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science.

Abstract: Transthyretin cardiac amyloidosis (ATTR and ATTRv) is an underrecognized cause of heart failure that results from myocardial deposition of misfolded protein (TTR or prealbumin). The diagnosis can be confirmed by uptake of 99mTc-pyrophosphate (99mTc-PYP) in the heart with serologic studies to rule out light chain disease. We present the case of a 70-year-old woman who underwent a 99mTc-PYP scan. Read More

Respir Med Case Rep 2022 18;37:101626. Epub 2022 Mar 18.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

We present the case of a 58-year-old man who presented with dyspnea, cough, and weight loss and was ultimately diagnosed with pulmonary amyloidosis and multiple myeloma. Diagnosis was achieved with a lung biopsy which showed AL amyloid deposits involving the interstitium, vessels, and airway. He was treated with cyclophosphamide, bortezomib, and dexamethasone but died prior to completing treatment. Read More

Circ Heart Fail 2022 Mar 25:CIRCHEARTFAILURE121009038. Epub 2022 Mar 25.

University of Pavia, Italy (G.M.).

Immunoglobulin light chain amyloidosis is a rare, multisystemic, phenotypically heterogenous disease affecting cardiovascular, renal, neurological, and gastrointestinal systems to varying degrees. Its underlying cause is a plasma cell dyscrasia characterized by misfolding of monoclonal immunoglobulin light chains which leads to aggregation and deposition of insoluble amyloid fibrils in target organs. Prognosis is primarily dependent on extent of cardiac involvement and depth of hematologic response to treatment. Read More

Diagnostics (Basel) 2022 Mar 3;12(3). Epub 2022 Mar 3.

Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Amyloidosis is a progressive infiltrative disease instigated by the extracellular deposition of amyloid fibrils in various organs such as the heart, kidney, and peripheral nerves. Cardiac amyloid deposits cause restrictive cardiomyopathy, leading to a poor prognosis in systemic amyloidosis. The most common etiologies of cardiac amyloidosis (CA) are immunoglobulin light chain deposits (AL-CA) and misfolded transthyretin deposits (ATTR-CA). Read More

CEN Case Rep 2022 Mar 22. Epub 2022 Mar 22.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 626, Rochester, NY, 14642, USA.

Light chain deposition disease (LCDD) is a form of monoclonal gammopathy of renal significance. The diagnosis is based on the immunofluorescence (IF) findings of linear monoclonal light chain staining of basement membranes throughout the kidney, which appear as non-organized, granular punctate to powdery electron dense deposits by electron microscopy (EM). Although "LCDD by IF only" without EM deposits has been well-described, LCDD identified by EM with negative IF is very rare and hardly mentioned in the literature. Read More

Hemasphere 2022 Mar 25;6(3):e687. Epub 2022 Feb 25.

Institute for Molecular Medicine Finland - FIMM, HiLIFE - Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Finland.

Immunoglobulin light-chain (AL) amyloidosis is a rare disease caused by clonal plasma cell secretion of misfolded light chains that assemble as toxic amyloid fibrils, depositing in vital organs including the heart and kidneys, causing organ dysfunction. Plasma cell-directed therapeutics are expected to reduce production of toxic light chain by eliminating amyloidogenic cells in bone marrow, thereby diminishing amyloid fibril deposition and providing the potential for organ recovery. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly releases alkylating agents inside tumor cells. Read More

Saudi J Kidney Dis Transpl 2021 Jul-Aug;32(4):1166-1170

Department of Nephrology, Liaquat National Hospital, Karachi, Pakistan.

About 3% of the population aged more than 50 years, is affected by monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition that may progress to lymphoproliferative disorders. Since MGUS does not represent the diseases associated with end organ damage, a new term, monoclonal gammopathy of renal significance (MGRS) is coined for the monoclonal gammopathies that are associated with renal disorders. MGRS is classified into various types, including monoclonal immunoglobulin deposition disease (MIDD) and proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID). Read More

Clin Kidney J 2022 Mar 28;15(3):417-424. Epub 2021 Sep 28.

Nephrology Department, Hospital del Mar, Barcelona, Spain.

Background: Renal manifestations of monoclonal gammopathies are of increasing interest among nephrologists. Typical manifestations include light chain cast nephropathy, amyloidosis or renal damage mediated by monoclonal immunoglobulin deposition. Podocytopathies in the setting of an underlying monoclonal gammopathy constitute a rare manifestation of these diseases and, although being described in the literature, remain a challenge since most data derive from case reports. Read More

Clin J Am Soc Nephrol 2022 04 24;17(4):527-534. Epub 2022 Feb 24.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, People's Republic of China.

Background And Objectives: Patients with monoclonal gammopathy and concomitant kidney diseases are frequently found in clinical practice. Some of them are diagnosed with monoclonal gammopathy of renal significance (MGRS) due to the presence of monoclonal Ig-related kidney injuries. This study aimed to investigate the histopathologic spectrum and clinical characteristics associated with MGRS in a large cohort of patients with monoclonal gammopathy and biopsy-proven kidney diseases from a single Chinese nephrology referral center. Read More

Cureus 2022 Jan 11;14(1):e21122. Epub 2022 Jan 11.

Nephrology, Shifa International Hospital, Islamabad, PAK.

Introduction Systemic amyloidosis can affect any organ in the body, but the kidney is the most commonly involved site. It is characterized by the extracellular deposition of insoluble fibrillar proteins. Amyloid deposits can be identified histologically by Congo red stain, which gives apple-green birefringence under polarized light. Read More

Ren Fail 2022 Dec;44(1):103-105

Department of Nephrology, Taixing People's Hospital, Taizhou, China.

Zhonghua Gan Zang Bing Za Zhi 2022 Jan;30(1):96-98

Department of Pathology, Guangzhou Kingmed Center for Clinical Laboratory, Guangzhou 510000, China.

Biochem Biophys Res Commun 2022 03 20;596:22-28. Epub 2022 Jan 20.

Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Science, Kyushu University, Japan. Electronic address:

AL amyloidosis is a life-threatening disease characterized by the deposition of amyloidogenic immunoglobulin light chain secreted from clonal plasma cells. Here we established an in-vitro screening system of amyloid inhibition of a variable domain in λ6 light chain mutant (Vλ6), Wil, and screened a food-additive compound library to identify compounds inhibiting the fibril formation. We found gossypetin and isoquercitrin as novel inhibitors. Read More

Ultrastruct Pathol 2022 Jan 1;46(1):130-138. Epub 2022 Feb 1.

Department of Pathology and Laboratory Medicine, Division of Renal Pathology and Electron Microscopy, University of Rochester Medical Center, Rochester, NY, USA.

The presence of myeloid bodies (MBs) is classically associated with Fabry disease (FD). However, MBs are also identified in patients without clinical evidence of FD. We attempt to further understand the clinicopathologic significance of incidental MBs in those without FD. Read More

ESC Heart Fail 2022 04 21;9(2):1186-1194. Epub 2022 Jan 21.

Department of Cardiology, University Hospital Zurich, University of Zurich, Raemistrasse 100, Zurich, 8091, Switzerland.

Aims: Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Read More

EMBO J 2022 02 12;41(4):e109108. Epub 2022 Jan 12.

Division of Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.

Haploinsufficiency of the progranulin (PGRN)-encoding gene (GRN) causes frontotemporal lobar degeneration (GRN-FTLD) and results in microglial hyperactivation, TREM2 activation, lysosomal dysfunction, and TDP-43 deposition. To understand the contribution of microglial hyperactivation to pathology, we used genetic and pharmacological approaches to suppress TREM2-dependent transition of microglia from a homeostatic to a disease-associated state. Trem2 deficiency in Grn KO mice reduced microglia hyperactivation. Read More

Saudi J Kidney Dis Transpl 2021 Mar-Apr;32(2):298-306

Department of Hematology, Army Hospital Research and Referral, Delhi Cantonment, New Delhi, India.

The occurrence of kidney diseases associated with a monoclonal gammopathy in the absence of symptomatic multiple myeloma is increasingly recognized. When the kidney is involved, the monoclonal etiology of these diseases results in clinical and laboratory features distinct from those of other disease, necessitating the nomenclature monoclonal gammopathy of renal significance (MGRS). The detection of these monoclonal diseases involving the kidney is important since they are poorly responsive to conventional immunosuppression and instead require clone-directed therapy. Read More

Ann Transl Med 2021 Nov;9(22):1658

Department of Cardiovascular Surgery, Tianjin Chest Hospital, Tianjin, China.

Background: Vascular calcification is related to many diseases. Iron has a certain relationship with endothelial cells and vascular calcification. The purpose of this study was to assess the effect of iron overload on endothelial cell calcification and related mechanisms through cell experiments. Read More

Rev Esp Patol 2022 Jan-Mar;55(1):4-11. Epub 2021 Aug 6.

Departamento de Patología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

Introduction: The kidney is one of the organs most frequently affected by disease processes which produce monoclonal immunoglobins, therefore renal morphological and immunopathological alterations should be clearly recognized.

Objective: To describe the pathological features of renal involvement in monoclonal gammopathies.

Material And Methods: A descriptive, retrospective and cross-sectional study of renal biopsies studied in a single center during a period of 14 years was carried out. Read More

Clin Neuropathol 2022 Mar-Apr;41(2):46-52

Aims: Cerebral amyloidomas (CAs) are mass-producing congophilic lesions most commonly due to λ light chain deposits, contrasting them with light chain deposition disease (LCDD) which has non-polarizable, often κ light chain deposition.

Materials And Methods: Although usual histological features are well known, we detail 3 recent CAs with unusual morphological findings and review the literature specifically for these features.

Results: Two women, aged 56 and 58 years, had right cerebral white matter CAs. Read More

Front Cardiovasc Med 2021 10;8:751293. Epub 2021 Dec 10.

National Amyloidosis Centre, Division of Medicine, University College London, London, United Kingdom.

Systemic amyloidosis is a rare, heterogenous group of diseases characterized by extracellular infiltration and deposition of amyloid fibrils. Cardiac amyloidosis (CA) occurs when these fibrils deposit within the myocardium. Untreated, this inevitably leads to progressive heart failure and fatality. Read More