Abstract
The Arctic mutation within the amyloid-β (Aβ) peptide causes Alzheimer disease. In vitro, Arctic-mutant Aβ forms (proto)fibrils more effectively than wild-type Aβ. 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 Aβ, even though Arctic mice had lower Aβ1-42/1-40 ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.
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Acknowledgements
We thank E. Koo for the CT15 antibody, P. Seubert for the 8E5 antibody, G.-Q. Yu and X. Wang for technical support, G. Howard and S. Ordway for editorial review, and D. McPherson and L. Manuntag for administrative assistance. This study was supported in part by United States Public Health Services grants AG11385, AG022074 and NS41787 to L.M. and National Institute on Aging-funded Training Grant T32 AG00278 (I.C.).
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Supplementary Fig. 1
Anti-Aβ antibodies 266 and 3D6 (used in Aβ ELISAs and western blotting) reacted similarly with synthetic Aβ-WT and Aβ-ARC peptides. (PDF 374 kb)
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Cheng, I., Palop, J., Esposito, L. et al. Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nat Med 10, 1190–1192 (2004). https://doi.org/10.1038/nm1123
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DOI: https://doi.org/10.1038/nm1123
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