Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition

Abstract

The highly diverse deposition pattern displayed by systemic amyloidoses, sometimes within the same amyloid disease, remains unexplained. The localized medin (AMed) amyloidosis develops from the precursor protein lactadherin and deposits in the media of the thoracic aorta in almost all individuals above 50 years of age. Given its high prevalence in the population, and the fact that systemic amyloidoses also deposit in the aorta, led us to investigate whether AMed amyloid could influence the tissue distribution of serum amyloid A derived (AA) amyloidosis. Seven aortas from patients with diagnosed systemic AA amyloidosis were investigated. Four displayed partial co-localization between medin and AA aggregates when examined with double-labeling immunofluorescence. Furthermore, in vitro studies showed that AMed amyloid-like fibrils promote the aggregation of protein AA into fibrils. The findings indicate that the highly frequent “senile” amyloidoses may have the potential to initiate fibril formation of the more uncommon amyloidoses by a cross-seeding mechanism.

Keywords::

• AA amyloid
• AMed amyloid
• aorta
• cross-seeding
• heterologous fibrils
• medin
• seed

Acknowledgements

We thank Jan Grawé and Siwei Peng for assistance with the confocal microscope and Åsa Edvinsson for her work in the laboratory.

Declaration of interest: This study was supported by the Swedish Research Council and a grant from the European Union FP6 Program to EURAMY.