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. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.