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阿尔茨海默病(Alzheimer disease,AD)是一种以神经认知和功能逐渐下降为特征的神经退行性疾病,主要病理标志是神经细胞间的β淀粉样蛋白(Amyloid-beta,Aβ)沉积和细胞内过度磷酸化tau蛋白聚集形成的神经元纤维缠结(neurofibrillary tangles,NFTs)。Aβ和NFTs能引起神经炎性改变,导致补体、细胞因子及其他的炎性因子释放。PET能够通过放射性生物标志物对神经炎性反应进行监测,其中,小胶质细胞(microglia,MG)激活后表达上调的一种转运蛋白(translocator protein,18kDa,TSPO),以前又称为外周型苯二氮受体(peripheral benzodiazepine receptor,PBR),其在炎症条件下主要存在于MG线粒体膜外表面,可利用放射性配体显像剂对其进行显像。
小胶质细胞在AD炎性机制中的作用及其常见PET显像剂的应用进展
Microglia's Alzheimer disease inflammatory mechanisms and progress of its common application in PET imaging agents
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摘要: 目前, 阿尔茨海默病(AD)被认为是一个连续动态的病理生理过程, 由β淀粉样蛋白斑(Aβ)的聚集引发一系列瀑布样的神经元变性反应, 使得神经元减少、突触功能降低, 导致认知功能障碍并最终发展为痴呆。除了Aβ的病理过程外, 许多研究表明, 神经炎性反应在AD的发病过程中起到了至关重要的作用。其中, 小胶质细胞(MG)在神经炎症病理过程中被激活且线粒体外膜表达上调一种转运蛋白(TSPO, 18kDa), 因此使用PET对MG上调的TSPO进行显像将有助于疾病的诊断和对治疗反应的监测。笔者对MG在神经炎性机制中的作用及其常用的PET显像剂进行综述。
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关键词:
- 阿尔茨海默病 /
- 小胶质细胞 /
- 正电子发射断层显像术 /
- 神经炎症反应 /
- 转运蛋白
Abstract: Alzheimer disease(AD) is considered a continuous and dynamic pathophysiological process.The disease is characterized by a series of neuronal degeneration reactions caused by amyloid plaque(i.e., amyloid-beta, A beta) aggregation leading to decreased neurons, reduced synaptic function, cognitive dysfunction, and, eventually, dementia.Besides the pathological process of A beta, numerous studies have shown that neuroinflammation performs a crucial function in the pathogenesis of AD.The in vivo use of PET to monitor the translocator protein(TSPO) upregulation of activated microglia during inflammation is helpful in diagnosing the disease and detecting treatment responses.This article will review the functions of microglia in neural inflammation and commonly used PET imaging agents.-
Key words:
- Alzheimer disease /
- Microglia /
- Positron-emission tomography /
- Neuroinflammation /
- Translocator protein
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