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阿尔茨海默病神经炎症的体内正电子发射断层扫描成像。

In vivo PET imaging of neuroinflammation in Alzheimer's disease.

机构信息

Unit of Neurology of Memory and Language, Centre de Psychiatrie et Neurosciences, INSERM UMR S894, Centre Hospitalier Sainte-Anne and Université Paris Descartes, Sorbonne Paris Cité, 75014, Paris, France.

UNIACT, NeuroSpin, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique, 91191, Gif-sur-Yvette, France.

出版信息

J Neural Transm (Vienna). 2018 May;125(5):847-867. doi: 10.1007/s00702-017-1731-x. Epub 2017 May 17.

Abstract

Increasing evidence suggests that neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer's disease (AD). Molecular imaging by PET may be a useful tool to assess neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.

摘要

越来越多的证据表明神经炎症参与了许多神经退行性疾病的病理生理学过程,尤其是阿尔茨海默病(AD)。正电子发射断层扫描(PET)分子成像可能是评估体内神经炎症的有用工具,有助于破译炎症过程在神经退行性疾病病理生理学中的复杂作用,并提供监测新治疗方法效果的潜在手段。为此,PET 研究的主要目标是 18 kDa 转位蛋白(TSPO),因为它在激活的小胶质细胞中过度表达。在本综述中,我们描述了最广泛使用的靶向 TSPO 的 PET 示踪剂、示踪剂定量的方法学问题,并总结了 TSPO PET 成像在 AD 以及与 AD 相关的神经退行性疾病、精神疾病和衰老中的研究结果。我们还简要描述了替代的 PET 靶点和成像方式,以研究神经炎症。最后,我们质疑 PET 成像数据在神经炎症在神经退行性疾病中的高度复杂和多方面作用背景下的意义。这篇综述的结论是,神经炎症的 PET 成像为破译 AD 病理生理学之谜以及监测新疗法的效果提供了一种有前途的方法。

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