Transmission of systemic amyloidosis

Keiichi Higuchi

Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University

Up to now, more than 36 amyloid diseases have been identified and each of the amyloidoses is associated with the aggregation of a particular precursor protein into amyloid fibrils. Amyloidosis is classified into two groups, systemic and localized amyloidosis. Precursor proteins of systemic amyloidosis circulating in the blood polymerize to amyloid fibrils and deposit in multiple organs of the body. In mice, apolipoprotein A-II (apoA-II) in serum high density lipoproteins (HDL) forms amyloid fibrils (AApoAII) in senile systemic amyloidosis (AApoAII amyloidosis) and acute phase HDL apolipoprotein SAA increases with inflammation forms amyloid fibrils (AA) and deposits in the liver, spleen, kidney and so on (AA amyloidosis). Intriguing data suggest that both amyloidoses could be transmitted in 4 levels, 1) protein to protein, 2) cell to cell, 3) organ to organ, and 4) animal to animal through a seeding / nucleation dependent polymerization mechanism. The transmission of amyloidosis among animals probably occurred by consumption of AApoAII fibrils which are excreted from affected animals into feces, milk, saliva and blood. Recently, seeding of transthyretin fibril (ATTR) formation was also demonstrated in vitro. AApoAII amyloid fibril formation is inhibited by blocking peptide which binds to the active ends of fibrils both in vitro and in vivo.

Address correspondence to Dr. Keiichi Higuchi, Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University (3-1-1 Asahi, Matsumoto 390-8621, Nagano, Japan)