Apolipoprotein E alters the processing of the β-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 β-amyloid peptides (Aβ). Here we show that, in contrast to APP^V717F Tg mice expressing apoE, APP^V717F Tg mice deficient in apoE develop anti-Aβ immunoreactive multifocal aggregates, which contain the β-cleaved C-terminal fragments (β-CTFs) of APP. Tg mice deficient in apoE also display altered levels of mature full-length APP, increased amounts of β-CTFs, as well as elevated levels of Aβ_1-40 and Aβ_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.