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衰老和痴呆中小胶质细胞激活的描述:使用[C]DPA713与[C](R)PK11195的正电子发射断层扫描

Depiction of microglial activation in aging and dementia: Positron emission tomography with [C]DPA713 versus [C]( R)PK11195.

作者信息

Yokokura Masamichi, Terada Tatsuhiro, Bunai Tomoyasu, Nakaizumi Kyoko, Takebayashi Kiyokazu, Iwata Yasuhide, Yoshikawa Etsuji, Futatsubashi Masami, Suzuki Katsuaki, Mori Norio, Ouchi Yasuomi

机构信息

1 Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

2 Department of Biofunctional Imaging, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

J Cereb Blood Flow Metab. 2017 Mar;37(3):877-889. doi: 10.1177/0271678X16646788. Epub 2016 Jul 21.

Abstract

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BP) in various brain regions using a first-generation translocator protein (TSPO) tracer CPK11195 and a second-generation tracer [C]DPA713. The BP levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer's disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [C]DPA713 BP in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when CPK11195 BP was used. Cognito-mnemonic scores were significantly correlated with [C]DPA713 BP levels in many brain regions, whereas CPK11195 BP failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than CPK11195. Positron emission tomography with [C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

摘要

健康老年人大脑中是否存在活化的小胶质细胞仍存在争议。我们旨在通过使用第一代转运体蛋白(TSPO)示踪剂[C](R)PK11195和第二代示踪剂[C]DPA713比较不同脑区的结合潜能(BP),来阐明衰老和痴呆中小胶质细胞活化的程度。使用简化参考组织模型估计的BP水平,在健康年轻人和老年人以及阿尔茨海默病(AD)患者之间进行比较,并与临床评分相关。方差分析显示,所有脑区中[C]DPA713 BP水平均呈现类别依赖性升高,且AD组显著增加,而使用[C](R)PK11195 BP时,各群组间未发现显著变化。认知记忆评分与许多脑区的[C]DPA713 BP水平显著相关,而[C](R)PK11195 BP与评分无相关性。如其他地方所述,本研究结果证实,第二代TSPO示踪剂[C]DPA713在衰老和神经元变性过程中对TSPO的敏感性均高于[C](R)PK11195。使用[C]DPA713的正电子发射断层扫描适用于描绘大脑皮层整体发生的体内小胶质细胞活化情况,而不受衰老和变性的影响。

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