Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils and protein A amyloid fibrils.
Murine senile [apolipoprotein A-II amyloid (AApoAII)] and reactive [protein A amyloid (AA)] amyloidosis are reported to be transmissible diseases via a seeding mechanism similar to that observed in the prion-associated disorders, although de novo amyloidogenesis and the progression of AApoAII or AA amyloidosis remain unclear. We examined the effect of co-injection of AApoAII and AA fibrils and multiple inflammatory stimuli in R1.P1-Apoa2(c) mice with the amyloidogenic Apoa2(c) allele. Both AApoAII and AA amyloidosis could be induced in this system, but the two types of amyloid fibrils preferentially promote the formation of the same type of fibrils while inhibiting the formation of the other. Furthermore, we demonstrate that AA or AApoAII amyloidosis could be cross-seeded by predeposited AApoAII or AA fibrils and that the predeposited amyloid fibrils were degraded when the fibril formation was reduced or stopped. In addition, a large proportion of the two amyloid fibrils colocalized during the formation of new fibrils in the spleen and liver. Thus, we propose that AApoAII and AA can both cross-seed and cross-compete with regard to amyloid formation, depending on the stage of amyloidogenesis. These results will aid in the clarification of the mechanisms of pathogenesis and progression of amyloid disorders.
Yan
Jingmin
J
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Japan.
Fu
Xiaoying
X
Ge
Fengxia
F
Zhang
Beiru
B
Yao
Junjie
J
Zhang
Huanyu
H
Qian
Jinze
J
Tomozawa
Hiroshi
H
Naiki
Hironobu
H
Sawashita
Jinko
J
Mori
Masayuki
M
Higuchi
Keiichi
K
D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D016633:Apolipoprotein A-II / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D013154:Spleen / Q000378:metabolism
D000682:Amyloid; D016633:Apolipoprotein A-II