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标题：Human apolipoprotein C-I expression in mice impairs learning and memory functions
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作者：Karlygash Abildayeva ; Jimmy F. P. Berbée ; Arjan Blokland 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：4
页码：856-869
DOI：10.1194/jlr.M700518-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD brains. Interestingly, apoC-I colocalized with β-amyloid (Aβ) in plaques in AD brains, and in vitro experiments revealed that aggregation of Aβ was delayed in the presence of apoC-I. Moreover, apoC-I was found to exacerbate the soluble Aβ oligomer-induced neuronal death. To establish a potential role for apoC-I in cognitive functions, we used human (h) APOC1 ^+/0 transgenic mice that express APOC1 mRNA throughout their brains and apoC-I protein in astrocytes and endothelial cells. The hAPOC1 ^+/0 mice displayed impaired hippocampal-dependent learning and memory functions compared with their wild-type littermates, as judged from their performance in the object recognition task ( P = 0.012) and in the Morris water maze task ( P = 0.010). ApoC-I may affect learning as a result of its inhibitory properties toward apoE-dependent lipid metabolism. However, no differences in brain mRNA or protein levels of endogenous apoE were detected between transgenic and wild-type mice. In conclusion, human apoC-I expression impairs cognitive functions in mice independent of apoE expression, which supports the potential of a modulatory role for apoC-I during the development of AD.