Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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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). ⋯ ρ and CSA can detect early nerve injury and correlate with electrophysiology in asymptomatic TTRv-carriers. T2app increases only in symptomatic ATTRv amyloidosis in whom it correlates with clinical scores and electrophysiology. Our results suggest that T2-relaxometry can provide biomarkers for disease- and therapy-monitoring in the future.
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Hereditary transthyretin-related amyloidosis is an autosomal dominant disorder. Recently, disease-modifying therapies (DMTs) have been developed. For at-risk individuals, genetic analysis aids in the early administration of medical care; however, few studies have evaluated the current status of genetic counselling and management of presymptomatic carriers of amyloidogenic variants. ⋯ Our study suggests the clinical utility of management using a combination of predictive testing and monitoring methods. Psychosocial support should be considered with collaboration between geneticists/genetic counsellors and psychologists. For a more optimised protocol for monitoring and designing future interventional trials in presymptomatic carriers, prospective cohort studies are necessary to clarify the natural history, particularly in the early stages of the disease.
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Numerous studies suggest a progressive accumulation of post-translationally modified peptides within amyloid fibrils, including isoaspartate (isoD) modifications. Here, we generated and characterised novel monoclonal antibodies targeting isoD-modified transthyretin (TTR). The antibodies were used to investigate the presence of isoD-modified TTR in deposits from transthyretin amyloidosis patients and to mediate antibody-dependent phagocytosis of TTR fibrils. ⋯ These antibodies label aged, non-native TTR deposits, leaving native TTR unattended and thereby potentially enabling new therapeutic approaches.