Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation

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Abstract

Mice deficient in BACE1 (beta-site APP cleaving enzyme 1) are healthy, fertile and appear normal in gross anatomy, tissue histology, hematology and clinical chemistry. BACE1−/− mice also hemizygous for an amyloid precursor protein (APP) transgene lack brain β-amyloid (Aβ) and β-secretase-cleaved APP C-terminal fragments (CTFs). These results provide validation of BACE1 as the major β-secretase in vivo and suggest that therapeutic inhibition of BACE1 for the treatment of Alzheimer's disease may be free of mechanism-based toxicity.

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Figure 1: BACE1 deficiency does not affect morphology of neural or non-neural tissues.
Figure 2: BACE1 deficiency abrogates brain Aβ.

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Correspondence to Robert Vassar.

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