出版社：American Society for Biochemistry and Molecular Biology
摘要：ABCA1-deficient mice have low levels of poorly lipidated apolipoproteinE (apoE) and exhibit increased amyloid load. To test whetherexcess ABCA1 protects from amyloid deposition, we crossed APP/PS1mice to ABCA1 bacterial artificial chromosome (BAC) transgenicmice. Compared with wild-type animals, the ABCA1 BAC led toa 50% increase in cortical ABCA1 protein and a 15% increasein apoE abundance, demonstrating that this BAC supports modestABCA1 overexpression in brain. However, this was observed onlyin animals that do not deposit amyloid. Comparison of ABCA1/APP/PS1mice with APP/PS1 controls revealed no differences in levelsof brain ABCA1 protein, amyloid, Aß, or apoE, despiteclear retention of ABCA1 overexpression in the livers of theseanimals. To further investigate ABCA1 expression in the amyloid-containingbrain, we then compared ABCA1 mRNA and protein levels in youngand aged cortex and cerebellum of APP/PS1 and ABCA1/APP/PS1animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1mice exhibited increased ABCA1 mRNA, but not protein, selectivelyin cortex. Additionally, ABCA1 mRNA levels were not increasedbefore amyloid deposition but were induced only in the presenceof extensive Aß and amyloid levels. These data suggestthat an induction of ABCA1 expression may be associated withlate-stage Alzheimer's neuropathology.Supplementary key words ATP binding cassette transporter A1 • apolipoprotein E • Alzheimer's disease • animal model
Abbreviations: Aß, amyloid-ß peptide; AD, Alzheimer's disease; apoE, apolipoprotein E; BAC, bacterial artificial chromosome; CNS, central nervous system; CSF, cerebrospinal fluid; LXR, liver X receptor; RXR, retinoic X receptor; Tg, transgenic; 24S-OH-Chol, 24S-hydroxycholesterol; 27-OH-Chol, 27-hydroxycholesterol
