Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.
Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.
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DOI：
10.1007/s00401-008-0481-0
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发表时间：
2009-03
影响因子：
12.7
通讯作者：
Fiala M
中科院分区：
文献类型：
--
作者：
Zaghi J;Goldenson B;Inayathullah M;Lossinsky AS;Masoumi A;Avagyan H;Mahanian M;Bernas M;Weinand M;Rosenthal MJ;Espinosa-Jeffrey A;de Vellis J;Teplow DB;Fiala M
寡聚淀粉样蛋白-β (Aβ)的神经元积累被认为是阿尔茨海默病（AD）患者神经元死亡的近端原因。血源性巨噬细胞可能通过向脑内迁移和吞噬Aβ来减轻神经元对Aβ的应激。我们测试了通过血脑屏障模型的迁移和输出，以及AD和正常受试者巨噬细胞对a β的吞噬和清除。由于Aβ充盈的巨噬细胞粘附在内皮层上，AD和正常巨噬细胞通过血脑屏障的Aβ输出均受到抑制。与正常受试者的巨噬细胞相比，AD巨噬细胞摄取和清除的Aβ较少，并在暴露于可溶性、原纤维或纤维性Aβ时发生凋亡。病变脑组织共聚焦显微镜显示，神经元和凋亡巨噬细胞中存在寡聚Aβ，这些细胞包围并浸润了嗜血性微血管，斑块和微血管壁中存在纤维状Aβ。与AD脑切片孵育后，正常受试者的单核细胞侵入神经元并上传寡聚物Aβ。总之，在AD患者中，巨噬细胞似乎将Aβ从神经元运送到血管，在血管中它们的凋亡可能释放纤维状Aβ，导致脑淀粉样血管病。
Neuronal accumulation of oligomeric amyloid-β (Aβ) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Aβ stress to neurons by immigration into the brain and phagocytosis of Aβ. We tested migration and export across a blood-brain barrier model, and phagocytosis and clearance of Aβ by AD and normal subjects’ macrophages. Both AD and normal macrophages were inhibited in Aβ export across the blood-brain barrier due to adherence of Aβ-engorged macrophages to the endothelial layer. In comparison to normal subjects’ macrophages, AD macrophages ingested and cleared less Aβ, and underwent apoptosis upon exposure to soluble, protofibrillar, or fibrillar Aβ. Confocal microscopy of stained AD brain sections revealed oligomeric Aβ in neurons and apoptotic macrophages, which surrounded and infiltrated congophilic microvessels, and fibrillar Aβ in plaques and microvessel walls. After incubation with AD brain sections, normal subjects’ monocytes intruded into neurons and uploaded oligomeric Aβ. In conclusion, in patients with AD, macrophages appear to shuttle Aβ from neurons to vessels where their apoptosis may release fibrillar Aβ, contributing to cerebral amyloid angiopathy.
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影响因子：
15.1
作者：
Kayed R;Head E;Sarsoza F;Saing T;Cotman CW;Necula M;Margol L;Wu J;Breydo L;Thompson JL;Rasool S;Gurlo T;Butler P;Glabe CG
通讯作者：
Glabe CG
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
5.3
作者：
Krajewska, M;Rosenthal, RE;Krajewski, S
通讯作者：
Krajewski, S
DOI：
10.1046/j.1365-2362.2002.00994.x
发表时间：
2002-05-01
影响因子：
5.5
作者：
Fiala, M;Liu, QN;Vinters, HV
通讯作者：
Vinters, HV
影响因子：
4.2
作者：
Majumdar, Amitabha;Chung, Haeyong;Maxfield, Frederick R.
通讯作者：
Maxfield, Frederick R.