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

Cheng, Irene H; Palop, Jorge J; Esposito, Luke A; Bien-Ly, Nga; Yan, Fengrong; Mucke, Lennart · Nat Med · 2004

basic_science · Level V

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Abstract

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.

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