Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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AA amyloidosis is a disease caused by extracellular deposition of insoluble β-pleated sheet fibrils composed of amyloid A (AA) protein, an amino (N)-terminal fragment of serum amyloid A (SAA). The deposits disrupt tissue structure and compromise organ function. Although the disease is systemic, deposition in kidney glomeruli is the most common manifestation. ⋯ The amyloid in 6 samples comprised peptides derived from SAA1 with few or none from SAA2, while the other two samples contained both SAA1- and SAA2-derived peptides. N-terminal AA peptides beginning with Arg1 as well as AA peptides starting with Ser2 were present in five of the eight samples, while all or nearly all of the N-terminal peptides in the other three samples lacked Arg1. These data demonstrate that multiple species of AA amyloid proteins can comprise the subunits in amyloid fibrils and raise the possibility that PTM may play a role in fibrillogenesis.
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The utilization and clinical impact of beta-blockers (BBs) in cardiac amyloidosis (CA) is largely unexplored. ⋯ Although some patients with CA may have indications for treatment with BB, their use is uncommon and those with more advanced disease tolerate BB poorly. Intolerance to BB in patients with cardiac AL is an indicator of poorer outcome.
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Neuropathy in transthyretin (ATTR) amyloidosis is frequently underdiagnosed, delaying effective treatment. Early detection of large- and small-nerve fiber damage via a comprehensive diagnostic algorithm impacts on clinical management. ⋯ This comprehensive test program gives new insights regarding the presence of neuropathy in ATTRv and ATTRwt, which impact on patient management.
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Cardiac transthyretin amyloidosis is a usually fatal form of restrictive cardiomyopathy for which clinical trials of treatments are ongoing. It is anticipated that quantitative nuclear medicine scintigraphy, which is experiencing growing interest, will soon be used to evaluate treatment efficacy. We investigated its utility for monitoring changes in disease load over a significant time period. ⋯ The spread of our results was notably high compared to the year-on-year increases. If left unaccounted for, variance may draw fallacious conclusions about changes in disease load. We therefore urge caution in drawing conclusions solely from nuclear medicine scintigraphy on a patient-by-patient basis, particularly across a short time period.
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A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.