Nature Neuroscience
4, 233 - 234 (2001)
doi:10.1038/85064
BACE1 is the major  -secretase for generation of A peptides by neuronsHuaibin Cai1, Yanshu Wang4, Diane McCarthy6, Hongjin Wen1, David R. Borchelt1, 3, Donald L. Price1, 2, 3, 5
& Philip C. Wong1, 51
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
2
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
3
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
4
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
5
Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
6
Ciphergen Biosystems, Fremont, California 94555, USA
Correspondence should be addressed to Philip C. Wong wong@jhmi.eduTwo  -secretases, BACE1 and BACE2, are involved in generation of Alzheimer's disease A peptides1,
2,
3. We report that secretion of A peptides (A1−40/42 and A11−40/42) is abolished in cultures of BACE1-deficient embryonic cortical neurons, and that whereas both human and murine BACE1 can cleave either human or murine -amyloid precursor protein (APP) at the +1 site of A, cleavage at the +11 site is species specific. We establish that BACE1 is the principal neuronal protease required to cleave APP at +1 and +11 sites that generate N-termini of A.
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