Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
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DOI：
10.1038/nm1058
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发表时间：
2004-07-01
期刊：
影响因子：
82.9
通讯作者：
Paul, SM
中科院分区：
文献类型：
--
作者：
Koistinaho, M;Lin, SZ;Paul, SM
我们先前已经证明，载脂蛋白E(APOE)促进脑内淀粉样蛋白的形成，并且APOE星形胶质细胞特异性表达显著影响阿尔茨海默病小鼠模型中淀粉样多肽(Abeta)的沉积。考虑到星形胶质细胞降解Abeta的能力，我们研究了APOE在星形胶质细胞介导的这种降解中的潜在作用。与培养的成年野生型小鼠星形胶质细胞相比，成年APOE(-/-)星形胶质细胞在体外不降解Abeta斑块脑切片中存在的Abeta。与APOE或Abeta的抗体或与低密度脂蛋白受体家族的拮抗剂RAP共同孵育，有效地阻止星形胶质细胞对Abeta的降解。相差显微镜和共聚焦显微镜显示，APOE(-/-)星形胶质细胞对Abeta沉积的反应或内化程度不同于野生型星形胶质细胞。因此，APOE似乎在星形胶质细胞降解和清除沉积的Abeta物种方面很重要，这一过程可能在阿尔茨海默病中受到损害。
We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-peptides (Abeta) in a mouse model of Alzheimer disease. Given the capacity of astrocytes to degrade Abeta, we investigated the potential role of Apoe in this astrocyte-mediated degradation. In contrast to cultured adult wild-type mouse astrocytes, adult Apoe(-/-) astrocytes do not degrade Abeta present in Abeta plaque-bearing brain sections in vitro. Coincubation with antibodies to either Apoe or Abeta, or with RAP, an antagonist of the low-density lipoprotein receptor family, effectively blocks Abeta degradation by astrocytes. Phase-contrast and confocal microscopy show that Apoe(-/-) astrocytes do not respond to or internalize Abeta deposits to the same extent as do wild-type astrocytes. Thus, Apoe seems to be important in the degradation and clearance of deposited Abeta species by astrocytes, a process that may be impaired in Alzheimer disease.