title: Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1)-mediated changes of endogenous amyloid beta in wild-type and transgenic mice in vivo.
abstract: Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1) initiates generation of amyloid beta (Abeta), a pathological hallmark of Alzheimer's disease. We investigated the impact of BACE1 protein level on endogenous Abeta. Endogenous Abeta and BACE1 protein levels were concurrently and significantly reduced during early life. However, Abeta levels were similar between BACE1 transgenic and wildtype mice. This suggests that BACE1 protein level has a minimal effect on the level of endogenous Abeta. Consequently, other factors must be involved in modulation of Abeta production in adult and ageing brain and investigation of such factors may yield therapeutic targets. Further, these results suggest that substantial inhibition of BACE1 in brain may be required for clinical benefit in Alzheimer's disease.
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Chiho
authors.initials: C
authors.lastname: Hirata-Fukae
authors.forename: Elkhansa Hassan
authors.initials: EH
authors.lastname: Sidahmed
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Gooskens
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Ilse
authors.initials: I
authors.lastname: Dewachter
authors.forename: Herman
authors.initials: H
authors.lastname: Devijver
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Matsuoka
mesh_terms: D000367:Age Factors; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human