LRP and senile plaques in Alzheimer's disease:: colocalization with apolipoprotein E and with activated astrocytes
LRP and senile plaques in Alzheimer's disease:: colocalization with apolipoprotein E and with activated astrocytes
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DOI：
10.1016/s0169-328x(02)00203-6
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发表时间：
2002-07-15
期刊：
影响因子：
--
通讯作者：
Hyman, BT
中科院分区：
文献类型：
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作者：
Arélin, K;Kinoshita, A;Hyman, BT
低密度脂蛋白受体相关蛋白（LRP）是一种多功能受体，存在于阿尔茨海默病（AD）的老年斑上。建议在β淀粉样蛋白（Abeta）合成和清除机制之间的平衡中发挥重要作用。其配体之一载脂蛋白 E (apoE) 也存在于老年斑上，并被认为是 AD 的危险因素，可能影响 Abeta 的沉积、纤维形成和清除。使用免疫组织化学，我们表明在 PDAPP 转基因小鼠和人类 AD 大脑中，LRP 仅存在于含有 apoE 的核心老年斑上。我们在神经元和反应性星形胶质细胞中检测到强烈的 LRP 染色，膜结合 LRP 的免疫染色显示与老年斑周围的线形星形胶质细胞过程共定位。 LRP 不存在于年轻转基因小鼠的斑块或 APOE 敲除小鼠的斑块中。由于与 AD 脑中 Abeta 沉积相关的 LRP 配体可能在诱导神经元和星形胶质细胞中 LRP 水平方面发挥重要作用，因此我们的研究结果支持这样的观点：apoE 可能参与 LRP（存在于精细星形胶质细胞过程中）的上调，并充当 LRP 和 Abeta 的局部支架蛋白。 LRP 的上调将增加 LRP 配体的清除以及 AP/ApoE 复合物的清除。 (C) 2002 Elsevier Science B.V. 保留所有权利。
The low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor which is present on senile plaques in Alzheimer's disease (AD). It is suggested to play an important role in the balance between amyloid beta (Abeta) synthesis and clearance mechanisms. One of its ligands, apolipoprotein E (apoE), is also present on senile plaques and has been implicated as a risk factor for AD, potentially affecting the deposition, fibrillogenesis and clearance of Abeta. Using immunohistochemistry we show that LRP was present only on cored, apoE-containing senile plaques, in both PDAPP transgenic mice and human AD brains. We detected strong LRP staining in neurons and in reactive astrocytes, and immunostaining of membrane-bound LRP showed colocalization with line astrocytic processes surrounding senile plaques. LRP was not present in plaques in young transgenic mice or in plaques of APOE-knockout mice. As LRP ligands associated with Abeta deposits in AD brain may play an important role in inducing levels of LRP in both neurons and astrocytes, our findings support the idea that apoE might be involved in upregulation of LRP (present in fine astrocytic processes) and act as a local scaffolding protein for LRP and Abeta. The upregulation of LRP would allow increased clearance of LRP ligands as well as clearance of AP/ApoE complexes. (C) 2002 Elsevier Science B.V. All rights reserved.