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Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence

Canetti, D; Nocerino, P; Rendell, NB; Botcher, N; Gilbertson, JA; Blanco, A; Rowczenio, D; ... Taylor, GW; + view all (2021) Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence. The Journal of Pathology , 255 (3) pp. 311-318. 10.1002/path.5770. Green open access

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Abstract

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in sixteen patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18–43 to p.20–43) in 16/24 trypsin-digested amyloid deposits, but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20–43 and to far lesser extent the N-terminal peptide, p.21–43 were fibrillogenic in vitro at physiological pH generating Congo red positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV associated pathologies.

Type: Article
Title: Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/path.5770
Publisher version: https://doi.org/10.1002/path.5770
Language: English
Additional information: Copyright © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: ApoA-IV amyloidosis, ApoA-IV sequence coverage, ApoA-IV signal-containing peptide, amyloid proteomics, fibrillogenic ApoA-IV signal-containing peptide, targeted mass spectrometry in serum
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10132407
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