(2020). DISCOVERY: prevalence of transthyretin (TTR) mutations in a US-centric patient population suspected of having cardiac amyloidosis: a comment. Amyloid. Ahead of Print.

Abstract Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having

Abstract Background Retinal angiopathy is a known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Optical coherence tomography angiography (OCT-A) is a recent noninvasive imaging technique, used in other retinal vascular diseases. Our purpose was to analyse subclinical changes in retinal vessels, with OCT-A, in patients with ATTRv amyloidosis. Methods Observational cross-sectional

Abstract Background Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort. Methods and results Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from

Objective To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. Methods sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP–

Till date, there had been no reported case of dialysis-related amyloidosis (DRA) associated with a β2-microglobulin variant. We report here a 41-year-old haemodialysis patient with systemic amyloidosis, exhibiting macroglossia and swelling salivary glands, uncommon clinical manifestations for DRA. Molecular analysis showed that the patient had a new variant of β2-microglobulin (V27M). Extracted amyloid

Lichen or macular localised cutaneous amyloidoses have long been described as keratinic amyloidoses and believed to be due to the deposition of cytokeratin peptides originating from epidermis in the dermal papillae. However, recently it was suggested that galectin-7 is the causative protein for this type of amyloidosis. This was based on the detection of galectin-7 in a biopsy from a patient diagnosed

Background Atrial fibrillation (AF) is common in patients with transthyretin cardiac amyloidosis (ATTR-CA). The optimal strategy to prevent strokes in patients with ATTR-CA and AF is unknown. Objectives To compare outcomes in patients with ATTR-CA and AF treated with warfarin versus novel oral anticoagulants (NOACs). Methods This study was a retrospective analysis of patients with ATTR-CA stratified

Abstract Transthyretin (TTR) tetramer dissociation is rate limiting for aggregation and subunit exchange. Slowing of TTR tetramer dissociation via kinetic stabiliser binding slows cardiomyopathy progression. Quadruplicate subunit exchange comparisons of the drug candidate AG10, and the drugs tolcapone, diflunisal, and tafamidis were carried out at 1, 5, 10, 20 and 30 µM concentrations in 4 distinct

The treatment of AL amyloidosis aims to eradicate the plasma cell clone and eliminate toxic free light chain production. Only in a minority of patients the plasma cell clone is completely eradicated; residual light chain production may still exist while clonal relapse may occur. We used sensitive next-generation flow cytometry (NGF) to detect minimal residual disease (MRD) in AL amyloidosis patients

Purpose To investigate the utility of the combined use of 11C-Pittsburgh compound B (11C-PiB) positron emission tomography (PET) imaging and 99mTc-pyrophosphate (99mTc-PYP) scintigraphy for detection and differentiation of three major types of cardiac amyloidosis, i.e. immunoglobulin light chain (AL), hereditary transthyretin (ATTRv), and wild-type transthyretin (ATTRwt) amyloidosis. Methods Whole-body

A rapid and deep haematologic response is fundamental in order to improve outcomes of patients with AL amyloidosis. We evaluated the impact of timing and depth of haematologic response at early time points (at 1 and 3 months from the start of therapy) in 227 consecutive previously untreated AL patients, who received bortezomib-based primary therapy. After 1 month of therapy, 30.5% had ≥VGPR, 28% PR

Introduction ATTRv amyloidosis is worldwide spread with endemic foci in Portugal and Sweden, Japan, Brazil, Maiorca, and Cyprus. A national Registry was developed to characterise the epidemiology and genotype-phenotype correlation of ATTRv amyloidosis in Italy and to allow a better planning of diagnostic and therapeutic services. Methods Fifteen Italian referral centres for amyloidosis spread all over

(2020). The sensitivity of DPD scintigraphy to detect transthyretin cardiac amyloidosis in V30M mutation depends on the phenotypic expression of the disease. Amyloid: Vol. 27, No. 3, pp. 174-183.

Abstract Background: Destabilised transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilising TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilised TTR. Recently, T119M was associated with extended lifespan and lower risk of cerebrovascular disease in a Danish cohort. We aimed to determine whether this finding

Abstract Background: Hereditary transthyretin amyloid (ATTRv) is a systemic amyloidosis with mainly neurological and cardiac symptoms. The aim of this study was to evaluate the outcome of [18F]Flutemetamol PET/CT-scan of the heart in long-term survivors with ATTRV30M amyloidosis. Methods: Twenty-one patients with ATTRV30M amyloidosis and predominantly neurological symptoms, mainly negative on cardiac

Background: Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use. Method: Patients treated with daratumumab monotherapy (2016–2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre. Results: Of 50 evaluable patients, haematological

(2020). Renal calcitonin amyloidosis in a patient with disseminated medullary thyroid carcinoma. Amyloid: Vol. 27, No. 3, pp. 213-214.

Background Hereditary transthyretin amyloidosis (ATTRV30M) is a rare disease caused by amyloid deposition and characterized by a heterogeneous presentation. Anticipation (AC) is described as the decrease in age at onset (AO) within each generation. Our aim was to study AC in a large number of ATTRV30M kindred from Majorca (Spain), and gain further insight into parent-of-origin effects. Methods In a

(2020). A case of novel amyloidosis: glucagon-derived amyloid deposition associated with pancreatic neuroendocrine tumour. Amyloid. Ahead of Print.

Objective: Patients with hereditary transthyretin (TTR) amyloidosis (hATTR) often experience disease progression after orthotopic liver transplant (POLT) due in part to wild type ATTR amyloid deposition. The management strategy is not defined. We propose that TTR gene silencing with an antisense oligonucleotide or a small interfering ribonucleic acid may be a treatment for these patients. Methods:

(2020). New visceral manifestations of fibrinogen alpha-chain amyloidosis. Amyloid. Ahead of Print.

The proteasome inhibitor, bortezomib, has become a backbone for the first line treatment of patients with AL amyloidosis who are not eligible for high dose melphalan and stem cell transplantation. The presence of t(11;14), seen in up to 40–60% of patients with AL amyloidosis, may be associated with poorer response when treated with bortezomib based regimens. This remains a critical distinction in light

(2020). From a misdiagnosis of anorexia nervosa to a dramatic patisiran-induced improvement in a patient with ATTRE89Q amyloidosis. Amyloid. Ahead of Print.

(2020). When to suspect transthyretin amyloidosis in cases of isolated vitreous opacities?. Amyloid. Ahead of Print.

Background: Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a multisystem disease that presents with polyneuropathy and/or cardiomyopathy. Methods: DISCOVERY, a multicenter screening study, enrolled patients with clinically suspected cardiac amyloidosis to determine the frequency of transthyretin (TTR) mutations and assess disease characteristics. Results: Of 1007 patients, the

Pomalidomide demonstrated activity in the treatment of AL amyloidosis in three phase II clinical trials. We evaluated the safety and efficacy of 28-day cycles of pomalidomide and dexamethasone in 153 previously treated patients with systemic AL amyloidosis. Ninety-nine (65%) were refractory to the last line of therapy and 54 (35%) had relapsed. The median number of previous lines of therapy was 3 (range:

Background: Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt.Methods: Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years

(2020). Two types of systemic amyloidosis in a single patient. Amyloid. Ahead of Print.

(2020). Electrochemical skin conductance values suggest frequent subclinical autonomic involvement in patients with AL amyloidosis. Amyloid: Vol. 27, No. 3, pp. 215-216.

(2020). Coexistence of wild type and hereditary ATTR amyloidosis in one family. Amyloid: Vol. 27, No. 1, pp. 71-72.

(2020). Misdiagnosis of hATTR amyloidosis: a single US site experience. Amyloid: Vol. 27, No. 1, pp. 69-70.

(2020). Isolated light chain deposition disease neuropathy in a patient with multiple myeloma. Amyloid: Vol. 27, No. 1, pp. 67-68.

Amyloidosis is a shared name for several rare, complex and serious diseases caused by extra-cellular deposits of different misfolded proteins. Accurate characterization of the amyloid protein is essential for patient care. Immunoelectron microscopy (IEM) and laser microdissection followed by tandem mass spectrometry (LMD-MS) are new gold standards for molecular subtyping. Both methods perform superiorly

Background: Cardiomyopathy is a major cause of death in patients with systemic transthyretin amyloidosis. Long term effect of therapy designed to inhibit hepatic production of the amyloid precursor has not been established in cardiomyopathy. The purpose of this study was to evaluate the long term safety and efficacy of transthyretin specific antisense oligonucleotide therapy, inotersen, in transthyretin

The novel class of compounds represented by lipid nanoparticle (LNP)-encapsulated siRNA formulations has an enormous potential to target disease, notably of the liver. Endocytosis of LNPs is believed to be mediated by APOE, an important serum protein of lipoprotein homeostasis. APOE polymorphisms affect binding to hepatic receptors and have been associated with development of specific disease. Here

Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical

Amyloidosis is an extremely rare event in rats. In this study, we report that lipopolysaccharide binding protein (LBP) is the most likely amyloidogenic protein in rat mammary amyloidosis. Histologically, corpora amylacea (CA) and stromal amyloid (SA) were observed in rat mammary glands, and needle-shaped amyloid (NA) was also observed on the surface or gap of CA and SA. Following surveillance in aged

Background: The diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (CR) or very good partial hematologic response (VGPR) but with renal organ relapse is not clear.Methods: We present eight patients with AL amyloidosis who had a repeat kidney biopsy performed.Results: AL amyloidosis was initially diagnosed by a kidney biopsy. All patients had a favorable response to treatment

Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected

From a clinical perspective, there is a need for a reliable and comprehensive list of diseases causing AA amyloidosis. This list could guide clinicians in the evaluation of patients with AA amyloidosis in whom an obvious cause is lacking. In this systematic review, a PubMed, Embase and Web of Science literature search were performed on causes of AA amyloidosis published in the last four decades. Initially

Background: The aim of the present prospective study (ClinicalTrials.gov Identifier: NCT02111538) was to assess the prognostic value of phase angle (PhA), derived from bioimpedance vectorial analysis (BIVA), in patients affected by systemic amyloid light-chain (AL) amyloidosis. Methods: One hundred-twenty seven consecutive newly diagnosed, treatment-naïve patients with histologically confirmed AL amyloidosis

Abstract Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated. Methods: Patients received either patisiran 0.3 mg/kg (n = 148) or placebo (n = 77) intravenously

Management of patients with relapsed or refractory (R/R) AL amyloidosis is complex. Some initial reports have shown positive results with daratumumab in heavily pre-treated AL amyloidosis patients. In this retrospective multicentric study, 38 patients (mean age 64 ± 9 years) with R/R AL amyloidosis treated with daratumumab were included. Cardiac and renal involvement was present in 76 and 74% of patients

(2020). Lysozyme amyloid: evidence for the W64R variant by proteomics in the absence of the wild type protein. Amyloid: Vol. 27, No. 3, pp. 206-207.

Abstract Objective: To study the outcome of patients with AL amyloidosis who were ineligible for high dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Methods: A real-life retrospective observational cohort study of Dutch patients with AL amyloidosis ineligible for HDM and ASCT was performed at the University Medical Center Groningen from January 2001 until April 2017. Primary

(2020). Geographic variation in public interest about amyloidosis in the United States and English speaking countries. Amyloid: Vol. 27, No. 3, pp. 210-212.

(2020). Fluorescence in situ hybridisation combined with CD138 immunomagnetic sorting is effective to identify cytogenetic abnormalities which play significant prognostic roles in Chinese AL amyloidosis patients. Amyloid: Vol. 27, No. 3, pp. 208-209.

Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy. Methods and results: Eighteen ATTRv (Val122Ile)

Background: Leukocyte chemotactic factor 2 (ALECT2) amyloidosis is one of the recently described types of amyloidosis. In this study, we reported the first large case series of renal ALECT2 amyloidosis in Chinese patients. Methods: We studied the prevalence, clinical characteristics, renal pathology, outcome and genetic features among seven patients diagnosed with renal ALECT2 amyloidosis at Peking

The Curated Protein Aggregation Database (CPAD) is a manually curated and open-access database dedicated to providing comprehensive information related to mechanistic, kinetic and structural aspects of protein and peptide aggregation. The database has been updated to CPAD 2.0 by significantly expanding datasets and improving the user-interface. Key features of CPAD 2.0 are (i) 83,098 data points on

We sought to evaluate how PROMIS patient-reported outcome (PRO) measures correlated with disease characteristics in systemic light chain (AL) amyloidosis patients at diagnosis. Newly diagnosed AL patients were recruited at two centres (N = 61). Patients completed the PROMIS Global Health v1.2, PROMIS-29 Profile v2.0 and Fatigue 8a v1.0. We assigned disease severity based on stage, presence of cardiac

Peripheral nerve involvement in immunoglobulin light chain (AL) amyloidosis is common, characterised by severe progressive mixed neuropathy with autonomic dysfunction but there is limited data on the implications and the characteristics of small nerve fibres dysfunction (SNFD). The aim of our prospective study was to evaluate SNFD and its clinical implications in newly diagnosed AL patients. Twenty-three

Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTR amyloidosis. Besides neurophysiological measures, there are no biomarkers to detect preclinical disease or monitor disease progression. CSF or plasma neurofilament light chain (pNfL) have recently been considered sensitive biomarkers to quantitate neuro-axonal damage in several disorders of the

(2020). Clinical manifestations in hereditary amyloidosis with the variant Glu54Gln transthyretin: a comment. Amyloid: Vol. 27, No. 2, pp. 144-144.

Background: Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) is a rare life-threatening disease that imposes considerable mortality and morbidity associated with increased costs, high social support and productivity losses. This study aims to estimate the societal costs and burden of ATTRv-PN. Methods: A cost-of-illness (COI) and burden of disease model were specified from a societal

Background: Patients with transthyretin (TTR) cardiac amyloidosis demonstrate cardiac cachexia with progression of their cardiomyopathy, which is characterised by malnutrition and a heightened inflammatory state. How best to measure this condition is less well characterised. We investigated differences in survival among patients with ATTR cardiac amyloidosis by nutritional status as defined by modified

AGel amyloidosis is a dominantly inherited systemic amyloidosis caused by mutations p.D214N or p.D214Y resulting in gelsolin amyloid (AGel) formation. AGel accumulates extracellularly in many tissues and alongside elastic fibres. AGel deposition associates with elastic fibre degradation leading to severe clinical manifestations, such as cutis laxa and angiopathic complications. We analysed elastic

(2020). Late-onset peripheral neuropathy in patients with wild type transthyretin amyloidosis (wtATTR) Amyloid: Vol. 27, No. 2, pp. 142-143.

A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden