Amyloid : the International Journal of Experimental and Clinical Investigation

BACKGROUND: Neurofilament light chain (NfL) is a biomarker of neuronal injury in hereditary ATTR (ATTRv) amyloidosis. However, the correlation between NfL and nerve conduction study (NCS), the standard test for ATTRv neuropathy, has not been investigated. OBJECTIVE: Elucidate the correlation between NfL and NCS parameters. METHODS: 227 serum NfL measurements were performed in 45 ATTRv patients, 5 asymptomatic carriers, and 12 controls. Among them, 177 simultaneous analyses of NCS and NfL were conducted in 45 ATTRv patients...

The ISA Nomenclature Committee met at the XIX International Symposium of Amyloidosis in Rochester, MN, 27 May 2024. The in-person event was followed by many electronic discussions, resulting in the current updated recommendations. The general nomenclature principles are unchanged. The total number of human amyloid fibril proteins is now 42 of which 19 are associated with systemic deposition, while 4 occur with either localised or systemic deposits. Most systemic amyloidoses are caused by the presence of protein variants which promote misfolding...

BACKGROUND: This study aimed to assess the prognostic value of cardiac magnetic resonance (CMR) variables and compare them with biological and echocardiographic markers in patients with AL cardiac amyloidosis (CA). METHODS: We conducted a prospective study across three tertiary centres, where patients underwent clinical examination, blood tests, echocardiography, and CMR. The primary endpoint was all-cause mortality. RESULTS: A total of 176 patients with AL CA were included, with a median age of 68 years (IQR 58-75)...

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No abstract text is available yet for this article.

BACKGROUND: To compare the efficacy of modified Ex-PRESS technique (ExP) versus Ahmed Glaucoma Valve (AGV) as primary surgery in hereditary transthyretin amyloidosis (ATTRv) secondary glaucoma. METHODS: Retrospective study at the national amyloidosis centre. Success was defined as an IOP ≥ 6 mmHg and ≤ 21 mmHg with no need for further glaucoma surgery or laser trabeculoplasty and without loss of light perception at the time of the last follow-up...

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF). METHODS: This epidemiology study assessed the international prevalence of ATTR-CM among patients aged ≥60 years with a history of HF, left ventricular ejection fraction (LVEF) >40%, an end-diastolic interventricular septum thickness (IVST) ≥12 mm, but without diagnosed amyloidosis, history of LVEF ≤40%, cardiomyopathy of known cause, severe valvular, or coronary heart disease...

No abstract text is available yet for this article.

BACKGROUND: Previously, T2-relaxation time (T2app ) and proton spin density (ρ) detected nerve injury in a small group of ATTRv amyloidosis. Here, we aim to quantify peripheral nerve impairment in a large cohort of symptomatic and asymptomatic ATTRv amyloidosis and correlate T2-relaxometry markers with clinical parameters and nerve conduction studies (NCS). METHODS: Eighty participants with pathologic variants of the transthyretin gene ( TTRv ) and 40 controls prospectively underwent magnetic resonance neurography...

No abstract text is available yet for this article.

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aβ associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M...

No abstract text is available yet for this article.

BACKGROUND: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA). OBJECTIVE: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid). METHODS: From 1996 to 2023 subcutaneous abdominal fat tissue aspirates were obtained from 1339 amyloidosis patients and 868 controls...

Translational research is key in advancing the diagnosis and therapy of systemic amyloidoses. This paper summarises our presentations at the ISA Workshop on Translation in Systemic Amyloidoses held in Athens on September 25-26, 2023. The critical advances made by the pioneers in the field are reviewed, with particular attention to the discoveries and developments of utmost importance to our understanding of what amyloid is and how the substance affects functions. Examples of translational research regarding the mechanisms of cardiac damage in light chain amyloidosis, the role of biomarkers in improving our understanding of the biology of the disease and patients' management, and the molecular mechanisms involved in the cytotoxicity are described...

OBJECTIVE: This study aims to delineate the clinical profiles of the hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) patients with A97S variant from southern China and the molecular characteristics of this mutant protein. METHODS: Fifteen ATTRv-PN patients with heterozygous A97S and one patient with homozygous A97S were included in the study. Serum TTR tetramer concentration was quantified through ultra-performance liquid chromatography. Stabilities of A97S-TTR were assessed through in vitro urea-mediated tryptophan fluorescence experiments, and nephelometry was employed in drug response assessment...

BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p...

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. METHODS AND RESULTS: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment...

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BACKGROUND: Early identification of immunoglobulin light-chain amyloidosis (AL) is crucial due to its rapid progression. Monoclonal light-chain (M-LC) testing is the first step in the diagnostic workup for patients with suspected cardiac amyloidosis (CA). We aimed to determine whether the time interval between the first CA suspicion and M-LC testing can be related to AL amyloidosis survival outcomes. METHODS: All patients ( n  = 94) with isolated cardiac AL amyloidosis diagnosed at our center between 2016 and 2020 were included...

BACKGROUND: Cardiac involvement in systemic light chain amyloidosis (AL) leads to chronic heart failure and is a major prognosis factor. Severe cellular defects are provoked in cardiac cells by tissue-deposited amyloid fibrils of misfolded free immunoglobulin light chains (LCs) and their prefibrillar oligomeric precursors. OBJECTIVE: Understanding the molecular mechanisms behind cardiac cell cytotoxicity is necessary to progress in therapy and to improve patient management...