Open this publication in new window or tab >>UCL, Natl Amyloidosis Ctr, London, England.;Royal Free Hosp, London, England..
UCL, Natl Amyloidosis Ctr, London, England.;Royal Free Hosp, London, England..
UCL, Natl Amyloidosis Ctr, London, England.;Royal Free Hosp, London, England..
Univ Pavia, Dept Mol Med Inst Biochem, Pavia, Italy..
UCL, Ctr Amyloidosis & Acute Phase Prot, Wolfson Drug Discovery Unit, Div Med, London, England.;Univ Pavia, Dept Mol Med Inst Biochem, Pavia, Italy..
Univ Udine, Dept Med DAME, Udine, Italy..
UCL, Ctr Amyloidosis & Acute Phase Prot, Wolfson Drug Discovery Unit, Div Med, London, England..
Univ Pavia, Dept Mol Med Inst Biochem, Pavia, Italy..
Univ Pavia, Dept Mol Med Inst Biochem, Pavia, Italy..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
UCL, Natl Amyloidosis Ctr, London, England.;Royal Free Hosp, London, England..
UCL, Natl Amyloidosis Ctr, London, England.;Royal Free Hosp, London, England..
UCL, Ctr Amyloidosis & Acute Phase Prot, Wolfson Drug Discovery Unit, Div Med, London, England.;Univ Pavia, Dept Mol Med Inst Biochem, Pavia, Italy..
UCL, Ctr Amyloidosis & Acute Phase Prot, Wolfson Drug Discovery Unit, Div Med, London, England..
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2021 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 255, no 3, p. 311-318Article in journal (Refereed) Published
Abstract [en]
Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 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 a 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. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Place, publisher, year, edition, pages
John Wiley & SonsWILEY, 2021
Keywords
ApoA-IV amyloidosis, ApoA-IV sequence coverage, ApoA-IV signal-containing peptide, amyloid proteomics, targeted mass spectrometry in serum, fibrillogenic ApoA-IV signal-containing peptide
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-469861 (URN)10.1002/path.5770 (DOI)000689701500001 ()34331462 (PubMedID)
2022-03-182022-03-182024-01-15Bibliographically approved