Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid?high-density lipoprotein
Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid?high-density lipoprotein
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可溶性LR11与β淀粉样蛋白竞争与脑脊液高密度脂蛋白的结合
DOI：
10.1016/j.cca.2018.11.024
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发表时间：
2019
影响因子：
5
通讯作者：
Miida Takashi
中科院分区：
文献类型：
--
作者：
Yano Kouji;Hirayama Satoshi;Misawa Naomi;Furuta Ayaka;Ueno Tsuyoshi;Motoi Yumiko;Seino Utako;Ebinuma Hiroyuki;Ikeuchi Takeshi;Schneider Wolfgang J.;Bujo Hideaki;Miida Takashi
LR11是低密度脂蛋白受体家族的一员，在神经元中高表达。一些细胞表面的LR11被裂解并分泌到脑脊液中，成为可溶性LR11(SLR11)。阿尔茨海默病(AD)患者，特别是载脂蛋白E4携带者，脑脊液sLR11含量高，脑脊液淀粉样蛋白(Aβ，Aβ)含量低。因此，我们评估了sLR11是否与脑脊液高密度脂蛋白结合，以及sLR11是否与Aβ竞争结合载脂蛋白E。采用非变性双向凝胶电泳法(N-2DGE)检测sLR11和apoE在脑脊液中的分布。结果AD患者脑脊液中sLR11的浓度高于对照组(用磷脂校正sLR11)。N-2DGE分析表明，sLR11和A-β融合了大量含有载脂蛋白E的脑脊液高密度脂蛋白。且在伴有载脂蛋白4/4的AD患者中，当β与ε结合较多时，与Aβ结合的载脂蛋白E较少。结论LR11与脑脊液高密度脂蛋白结合，并与Aβ竞争结合，提示sLR11通过脑脊液高密度脂蛋白影响A apoE清除。
BackgroundLR11 is a member of the low-density lipoprotein (LDL) receptor family with high expression in neurons. Some cell surface LR11 is cleaved and secreted into the cerebrospinal fluid (CSF) as soluble LR11 (sLR11). Patients with Alzheimer's disease (AD), particularly apolipoprotein E4 carriers, have high CSF–sLR11 and low CSF–amyloid β (Aβ) concentrations. Therefore, we assessed whether sLR11 is bound to CSF–high-density lipoprotein (HDL) and whether sLR11 competes with Aβ in binding to apoE in CSF–HDL.MethodsWe measured CSF–sLR11 concentrations (50 controls and 16 patients with AD) using enzyme immunoassay. sLR11 and apoE distribution in the CSF was evaluated using non-denaturing two-dimensional gel electrophoresis (N–2DGE). ApoE bound to sLR11 or Aβ was identified using co-immunoprecipitation assay.ResultsCSF–sLR11 concentrations were higher in patients with AD than controls (adjusted for sLR11 using phospholipid). N–2DGE analysis showed that sLR11 and Aβ comigrated with a large apoE-containing CSF–HDL. Moreover, fewer apoE was bound to Aβ when a higher amount of apoE was bound to sLR11 in patients with AD who presented with ε4/4.ConclusionsLR11 binds to CSF–HDL and competes with Aβ in binding to apoE in CSF–HDL, indicating that sLR11 affects Aβ clearance via CSF–HDL.