Fibrilization in mouse senile amyloidosis is fibril conformation- dependent

Keiichi Higuchi, Kumiko Kogishi, Jing Wang, Xia Chen, Takuya Chiba, Takatoshi Matsushita, Yoshinobu Hoshii, Hiroo Kawano, Tokuhiro Ishihara, Tadaaki Yokota, Masanori Hosokawa

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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, as 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. No amyloid deposition was observed in mice having an amyloid-resistant apoA-II gene (Apoa2(b)) even 3 months after AApoAII injection. Significantly less amyloid deposition was observed in mice having both types of apoA-II genes heterozygously (Apoa2(b/c)). These findings suggest 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 vivo. Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in vivo; it may be useful in both elucidating the pathogenesis of amyloidosis and developing effective therapeutic modalities to treat this disease.

Original languageEnglish
Pages (from-to)1535-1542
Number of pages8
JournalLaboratory Investigation
Volume78
Issue number12
Publication statusPublished - 1998 Dec 1

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Higuchi, K., Kogishi, K., Wang, J., Chen, X., Chiba, T., Matsushita, T., Hoshii, Y., Kawano, H., Ishihara, T., Yokota, T., & Hosokawa, M. (1998). Fibrilization in mouse senile amyloidosis is fibril conformation- dependent. Laboratory Investigation, 78(12), 1535-1542.