Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation

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 Abeta(1-42/1-40) ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.