Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1)-mediated changes of endogenous amyloid beta in wild-type and transgenic mice in vivo.
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.
Hirata-Fukae
Chiho
C
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
Sidahmed
Elkhansa Hassan
EH
Gooskens
Thomas P
TP
Aisen
Paul S
PS
Dewachter
Ilse
I
Devijver
Herman
H
Van Leuven
Fred
F
Matsuoka
Yasuji
Y
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
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human