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

Y Luo, B Bolon, S Kahn, BD Bennett… - Nature …, 2001 - nature.com
Y Luo, B Bolon, S Kahn, BD Bennett, S Babu-Khan, P Denis, W Fan, H Kha, J Zhang
Nature neuroscience, 2001nature.com
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 …
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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