Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

Abstract

AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine⅐HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction.feces ͉ transmissibility

Transmission of Systemic AA Amyloidosis in Animals

“…While AA amyloid fibrils were not detected in cheetah urine, cheetah feces unexpectedly contained AA amyloid fibrils that differed from those seen in the liver. Compared with liver amyloid fibrils, fecal amyloid fibrils had a smaller molecular weight due to deletion of both N-and C-terminal sequences, a shorter and finer fibrillar shape on electron microscopy, 82 and increased sensitivity to denaturation treatments, such as incubation in 6 M guanidine hydrochloride solution. Interestingly, comparison of the transmissibility of fecal and liver AA amyloid fibrils using the mouse experimental AA amyloidosis system showed that the fecal amyloid fibrils from the cheetah exhibited significantly greater transmissibility.…”

“…52 We examined the possibility of horizontal transfer or transmission of AA amyloidosis in a group of captive cheetah with severe AA amyloid deposition in the kidney, liver, and spleen, as well as in other organs. 82 The AA fibril protein isolated from the liver was equivalent to the N-terminal part of the precursor protein SAA (the longest AA peptides consisted of amino acids 1-93 of the 111-amino acid, full-length precursor protein). While AA amyloid fibrils were not detected in cheetah urine, cheetah feces unexpectedly contained AA amyloid fibrils that differed from those seen in the liver.…”

The aggregation of mutant p53 produces prion-like properties in cancer

“…43 Laboratory experiments demonstrated the host-to-host transmission of AA amyloidosis. 44 However, no epidemiological data support the natural host-tohost transmission of any of these diseases other than TSEs.…”

Mouse Models to Study Systemic Amyloidoses: Is Prion-Like Transmission a Common Pathogenic Mechanism?

“…We hypothesize that the propagation of AA amyloidosis among captive cheetah populations may depend on a horizontal transmission pathway (B. Zhang et al, 2008). Captive cheetahs with severe AA amyloidosis were studied.…”