Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.
J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):21-8. doi: 10.1136/jnnp-2015-311336. Epub 2015 Sep 18.
We are still very limited in management strategies for dementia, and establishing effective disease modifying therapies based on amyloid or tau remains elusive. Neuroinflammation has been increasingly implicated as a pathological mechanism in dementia and demonstration that it is a key event accelerating cognitive or functional decline would inform novel therapeutic approaches, and may aid diagnosis. Much research has therefore been done to develop technology capable of imaging neuroinflammation in vivo. The authors performed a systematic search of the literature and found 28 studies that used in vivo neuroimaging of one or more markers of neuroinflammation on human patients with dementia. The majority of the studies used positron emission tomography (PET) imaging of the TSPO microglial marker and found increased neuroinflammation in at least one neuroanatomical region in dementia patients, most usually Alzheimer's disease, relative to controls, but the published evidence to date does not indicate whether the regional distribution of neuroinflammation differs between dementia types or even whether it is reproducible within a single dementia type between individuals. It is less clear that neuroinflammation is increased relative to controls in mild cognitive impairment than it is for dementia, and therefore it is unclear whether neuroinflammation is part of the pathogenesis in early stages of dementia. Despite its great potential, this review demonstrates that imaging of neuroinflammation has not thus far clearly established brain inflammation as an early pathological event. Further studies are required, including those of different dementia subtypes at early stages, and newer, more sensitive, PET imaging probes need to be developed.
我们在痴呆症的管理策略方面仍然非常有限,基于淀粉样蛋白或 tau 建立有效的疾病修饰疗法仍然难以实现。神经炎症作为痴呆症的一种病理机制越来越受到关注,如果能证明其是加速认知或功能下降的关键事件,将为新的治疗方法提供信息,并可能有助于诊断。因此,许多研究都致力于开发能够在体内对神经炎症进行成像的技术。作者对文献进行了系统检索,发现了 28 项研究,这些研究使用了一种或多种神经炎症标志物的体内神经影像学方法,对患有痴呆症的人类患者进行了研究。大多数研究都使用了 TSPO 微胶质标志物的正电子发射断层扫描(PET)成像,发现痴呆症患者至少在一个神经解剖区域的神经炎症增加,与对照组相比,最常见的是阿尔茨海默病,但迄今为止发表的证据并不表明神经炎症的区域分布在痴呆症类型之间存在差异,甚至在个体之间的单一痴呆症类型内是否具有可重复性。与痴呆症相比,轻度认知障碍患者的神经炎症增加相对对照组而言并不明显,因此尚不清楚神经炎症是否是痴呆症早期发病机制的一部分。尽管具有巨大的潜力,但该综述表明,神经炎症成像尚未明确将大脑炎症确立为早期病理事件。需要进一步研究,包括在早期对不同的痴呆症亚型进行研究,以及开发新的、更敏感的 PET 成像探针。