Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
-
Amyloid signature proteins such as serum amyloid P component, apolipoprotein E (ApoE), and ApoA-IV generally co-localise with amyloid, regardless of the types of amyloid precursor protein or the organs. Most of these proteins derive from serum and have reportedly been involved in amyloid fibril formation and stabilisation, as well as in excretion and degradation of amyloid precursor proteins. However, the processes and mechanisms by which these specific proteins deposit together with amyloid fibrils have not been clarified. ⋯ Our in vitro results suggest that amyloid signature proteins coexist with amyloid primarily dependent on the binding of each serum protein, in the extracellular fluid, to amyloid fibrils.
-
We aimed at investigating whether functional and morphometric tests assessing small-fibre damage, ie quantitative sensory testing, Sudoscan and skin biopsy, reliably reflect neuropathic pain and autonomic symptoms in patients with late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). ⋯ Our findings indicate that functional test parameters reliably reflect neuropathic pain and autonomic symptoms related to small-fibre damage. These findings might help to identify clinically useful biomarkers to assess patient follow-up.
-
Cardiac amyloidosis is a severe condition leading to restrictive cardiomyopathy and heart failure. Mass spectrometry-based methods for cardiac amyloid subtyping have become important diagnostic tools but are currently used only in a few reference laboratories. Such methods include laser-capture microdissection to ensure the specific analysis of amyloid deposits. Here we introduce a direct proteomics-based method for subtyping of cardiac amyloidosis. ⋯ Cardiac amyloidosis can be successfully subtyped without the prior enrichment of amyloid deposits with laser microdissection.
-
Assess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis). ⋯ Patisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function.(ClinicalTrials.gov number, NCT01960348).
-
Biochemical characterisation of transthyretin variant TTR Y78F showed that this variant adopts a tetrameric conformation as normal TTR but exhibits some of the characteristics of an intermediate structure in the fibrillogenesis pathway. It was hypothesised that native Y78F might represent an early event in TTR amyloidogenesis. We immunised TTR knock out mice with recombinant variant TTR Y78F. ⋯ At the same time, this clone was negative for TTR V30M, soluble wild type protein or TTR T119M. The reactivity increased with oligomer formation and decreased as mature fibrils grow. After size exclusion chromatography (SEC) followed by sandwich ELISA and native immunoblotting, the mAb recognised two peaks (i) peak 1 present in acidified and in soluble variant proteins preparations with material above 146 KDa (ii) peak 2 only present in soluble L55P and S52P TTR preparations with material between 66 and 146 KDa. mAb CE11 may be a potential tool to survey therapeutical agents against TTR aggregation.