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

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 super(-/-) mice also hemizygous for an amyloid precursor protein (APP) transgene lack brain b-amyloid (Ab) and b-secretase-cleaved APP C-terminal fragments (CTFs). These results provide validation of BACE1 as the major b-secretase in vivo and suggest that therapeutic inhibition of BACE1 for the treatment of Alzheimer's disease may be free of mechanism-based toxicity.