Amyloidogenic potential of foie gras

Abstract

The human cerebral and systemic amyloidoses and prion-associated spongiform encephalopathies are acquired or inherited protein folding disorders in which normally soluble proteins or peptides are converted into fibrillar aggregates. This is a nucleation-dependent process that can be initiated or accelerated by fibril seeds formed from homologous or heterologous amyloidogenic precursors that serve as an amyloid enhancing factor (AEF) and has pathogenic significance in that disease may be transmitted by oral ingestion or parenteral administration of these conformationally altered components. Except for infected brain tissue, specific dietary sources of AEF have not been identified. Here we report that commercially available duck- or goose-derived foie gras contains birefringent congophilic fibrillar material composed of serum amyloid A-related protein that acted as a potent AEF in a transgenic murine model of secondary (amyloid A protein) amyloidosis. When such mice were injected with or fed amyloid extracted from foie gras, the animals developed extensive systemic pathological deposits. These experimental data provide evidence that an amyloid-containing food product hastened the development of amyloid protein A amyloidosis in a susceptible population. On this basis, we posit that this and perhaps other forms of amyloidosis may be transmissible, akin to the infectious nature of prion-related illnesses.

Fig. 1.

AA deposition in foie gras. (a) Large venule surrounded by residual, extensively vacuolated fatty hepatic tissue (hematoxylin/eosin stain). (b) Green birefringent amyloid deposits in the blood vessel wall (Congo red stain). (c) Immunohistochemical identification of vascular AA amyloid. (Scale bar, 62 μm.)

Fig. 2.

Tissue fragment with amyloid in duck pâté. Congo red stain.

Fig. 3.

Ultrastructural and chemical characterization of amyloid extracted from foie gras. (a) Fibrillar nature of proteins contained in the pellet (electron micrograph, negative uranyl acetate stain). (Scale bar, 200 nm.) (b) SDS/PAGE of congophilic components extracted from duck foie gras and the spleen of a mouse with AA amyloidosis (Coomassie blue stain). The M_r values of the standard proteins are given; arrows show the location of AA-containing protein bands. (c) Comparison of the amino acid sequence of duck foie gras AA amyloid with that of duck SAA (9). Homologous residues are indicated by dashes.

Fig. 4.

AEF activity of foie gras. Hepatic and splenic amyloid deposits found in hIL-6 transgenic mice 8 wk after they were injected (a) or gavaged (b) with AA fibrils extracted from foie gras. The extent of amyloid burden in the liver (■), spleen (▨), kidney (□), and pancreas (▩) is as indicated. (Scale bars, 100 μm.)