Expression of human β‐secretase in the mouse brain increases the steady‐state level of β‐amyloid

β‐Site APP‐cleaving enzyme (BACE) initiates the processing of the amyloid precursor protein (APP) leading to the generation of β‐amyloid, the main component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a type I transmembrane aspartyl protease and is responsible for the β‐secretase cleavage of APP producing different endoproteolytic fragments referred to as the carboxy‐terminal C99, C89 and the soluble ectodomain sAPPβ. Here we describe two transgenic mouse lines expressing human BACE in the brain. Overexpression of BACE augments the amyloidogenic processing of APP as demonstrated by decreased levels of full‐length APP and increased levels of C99 and C89 in vivo. In mice expressing huBACE in addition to human APP wild‐type or carrying the Swedish mutation, the induction of APP processing characterized by elevated C99, C89 and sAPPβ, results in increased brain levels of β‐amyloid peptides Aβ40 and Aβ42 at steady‐state.

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