Apolipoprotein E alters the processing of the beta-amyloid precursor protein in APP(V717F) transgenic mice.
We have recently reported a critical role for apolipoprotein E (apoE) in the process of amyloid deposition and neuritic plaque formation in APP(V717F) transgenic (Tg) mice, an animal model of Alzheimer's disease (AD). In the present study, we have investigated whether the presence or absence of apoE alters the processing of the amyloid precursor protein (APP) to various fragments, including the beta-amyloid peptides (Abeta). Here we show that, in contrast to APP(V717F) Tg mice expressing apoE, APP(V717F) Tg mice deficient in apoE develop anti-Abeta immunoreactive multifocal aggregates, which contain the beta-cleaved C-terminal fragments (beta-CTFs) of APP. Tg mice deficient in apoE also display altered levels of mature full-length APP, increased amounts of beta-CTFs, as well as elevated levels of Abeta(1-40) and Abeta(1-42) in an age- and region-dependent manner when compared to Tg mice expressing apoE. Taken together, these data support a role for apoE in APP processing in vivo.
Dodart
Jean-Cosme
JC
Neuroscience Discovery Research, Eli Lilly and Company, Indianapolis, IN 46285, USA. jcdodart@lilly.com
Bales
Kelly R
KR
Johnstone
Edward M
EM
Little
Sheila P
SP
Paul
Steven M
SM
D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010649:Phenylalanine / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D014633:Valine / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D010649:Phenylalanine; D014633:Valine