Transmissibility of mouse AApoAII amyloid fibrils: inactivation by physical and chemical methods

Abstract

AApoAII amyloid fibrils have exhibited prion-like transmissibility in mouse senile amyloidosis. We have demonstrated that AApoAII is extremely active and can induce amyloidosis following doses less than 1 pg. We tested physical and chemical methods to disrupt AApoAII fibrils in vitro as determined by thioflavin T binding and electron microscopy (EM) as well as inactivating the transmissibility of AApoAII fibrils in vivo. Complete disruption of AApoAII fibrils was achieved by treatment with formic acid, 6 M guanidine hydrochloride, and autoclaving in an alkaline solution. Injection of these disrupted AApoAII fibrils did not induce amyloidosis in mice. Disaggregation with 6 M urea, autoclaving, and alkaline solution was incomplete, and injection of these AApoAII fibrils induced mild amyloidosis. Treatment with formalin, delipidation, freeze-thaw, and RNase did not have any major effect. A distinct correlation was obtained between the amounts of amyloid fibrils and the transmissibility of amyloid fibrils, thereby indicating the essential role of fibril conformation for transmission of amyloidosis. We also studied the inactivation of AApoAII fibrils by several organic compounds in vitro and in vivo. AApoAII amyloidosis provides a valuable system for studying factors that may prevent transmission of amyloid disease as well as potential novel therapies.

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

“…A few recent studies have shown that AA-containing extracts also had amyloid-inducing activity when administered orally to mice (36,37). In AApoAII amyloidosis, we reported that an oral administration of AApoAII amyloid fibrils induced amyloidosis in recipient mice (38). Thus, it is plausible that oral ingestion of AA-containing fecal matter caused amyloid deposition in the cheetah population.…”

“…The lyophilized fibrils were dissolved in DW (1.0 mg/ml) and used immediately for injection (42). The other lyophilized AA fibrils were treated with 88% formic acid for 8 h at room temperature followed by dialysis against DW for 6 h before injection (38).…”

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

“…Thus the period for detection decreased to less than 1 month compared to Tg À/À mice. 54 Since fibrilization of several kinds of amyloid proteins is nucleation-dependent, self-and cross-seeding by amyloid fibrils and amyloid fibril-like materials is thought to be a key factor for the progress of amyloidosis. To elucidate the pathogenesis of amyloidosis and to prevent it, it is necessary to improve the current bio-assay system for detection of amyloid fibrils and amyloidogenic materials in the environment.…”

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

“…Acceleration was slowed by 6 M urea or by autoclaving, and it was not changed by formalin, DNAse or RNAse treatments. This finding revealed that transmissibility of AApoAII depends on fibril conformation (H. Zhang et al, 2006). .P1-Apoa2 c mice that were kept in the same cage with mice having amyloidosis for 3 months developed amyloidosis.…”