| Research Abstract |
Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2^c). After AApoAII injection, amyloid deposition occurred rapidly, and advanced in an accelerated manner observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high density lipoprotein (HDL) and denatured apoA-II monomer which have the same primary structure but without a fibril conformation did not induce amyloidosis. These findings suggested that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in viva.
We injected AApoAII amyloid fibrils isolated from the liver of an old R1.P1-Apoa2^c mouse into the stomach
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of young mice using feeding needles for five consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for three months with old mice that had severe amyloidosis. Detection of AApoAII in feces of old mice suggested the transmission by eating of feces.
Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in viva. Further, we substantiated the transmissibility of AApoAII amyloidosis and presented the unique pathogenesis of amyloidosis "oral transmission of amyloid fibril conformation", that is, invasion of exogenous amyloid fibrils acts as seeds and changes the conformation of endogenous amyloid protein to polymerize into amyloid fibrils. Less
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