Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation.
The Arctic mutation within the amyloid-beta (Abeta) peptide causes Alzheimer disease. In vitro, Arctic-mutant Abeta forms (proto)fibrils more effectively than wild-type Abeta. We generated transgenic mouse lines expressing Arctic-mutant human amyloid precursor proteins (hAPP). Amyloid plaques formed faster and were more extensive in Arctic mice than in hAPP mice expressing wild-type Abeta, even though Arctic mice had lower Abeta(1-42/1-40) ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.
Cheng
Irene H
IH
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA.
Palop
Jorge J
JJ
Esposito
Luke A
LA
Bien-Ly
Nga
N
Yan
Fengrong
F
Mucke
Lennart
L
D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D058225:Plaque, Amyloid / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor