The Arctic mutation within the amyloid- (A) peptide causes Alzheimer disease. In vitro, Arctic-mutant A forms (proto)fibrils more effectively than wild-type A. 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 A, even though Arctic mice had lower A1-42/1-40 ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.
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