Is Prion-like transmission a common pathogenic mechanism for systemic amyloidoses ?: Cheetah and mouse amyloidoses

Keiichi Higuchi

Department of Aging Biology, Institute of Pathogenesis and Disease Prevention

Currently, more than 26 amyloid diseases have been identified such as the prion diseases, Alzheimer's disease, type 2 diabetes and various systematic amyloidoses. In mice, apolipoprotein A-II (apoA-II) in serum high density lipoproteins forms amyloid fibrils (AApoAII) in age-associated systemic amyloidosis (AApoAII amyloidosis). AA amyloidosis, known as reactive amyloidosis associated with inflammation, is generally recognized as the predominant form of systemic amyloidosis that occurs in humans, mice, cheetahs and domestic animals. These amyloidoses are characterized by the systemic deposition of extracellular fibrils composed of apoA-II in AApoAII amyloidosis or serum amyloid A (SAA) in AA amyloidosis. In most species, AApoAII and AA amyloidosis occurs sporadically associated with aging (AApoAII amyloidosis) and chronic inflammation (AA amyloidosis). However, recent intriguing data suggest that both amyloidoses could be transmitted by a prion-like infectious process through a seeding-nucleation mechanism. In these amyloidoses, AApoAII and AA amyloid fibrils induces the conformational change of native apoA-II and SAA to the amyloid fibrils and causes diseases in the affected individuals. The propagation of amyloidosis among animals probably occurred by consumption of AApoAII fibrils found in feces, milk and saliva excreted from affected mice and AA fibrils in feces in captive cheetahs.

Address correspondence to Dr. Keiichi Higuchi, Department of Aging Biology, Institute of Pathogenesis and Disease Prevention (3-1-1 Asahi, Matsumoto 390-8621, Japan)