Microglial activation and amyloid deposition in mild cognitive impairment A PET study
Microglial activation and amyloid deposition in mild cognitive impairment A PET study
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DOI：
10.1212/01.wnl.0000338622.27876.0d
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发表时间：
2009-01-06
期刊：
影响因子：
9.9
通讯作者：
Brooks, D. J.
中科院分区：
文献类型：
--
作者：
Okello, A.;Edison, P.;Brooks, D. J.
背景：激活的小胶质细胞聚集在β-淀粉样蛋白（A β）斑块周围，可能在阿尔茨海默病（AD）的发病机制中发挥作用。因此，它们是AD及其前驱症状遗忘型轻度认知损害（MCI）的潜在治疗靶点。目的：采用（11）C-（R）-PK 11195和（11）C-PIB PET在体内表征遗忘型MCI患者中小胶质细胞活化和淀粉样蛋白沉积的分布。方法：14例MCI患者接受了（11例）C-（R）-PK 11195和（11例）C-PIB PET，并进行了心理测量学测试。结果如下：14例MCI患者中有7例（50%）皮质（11）C-PIB保留增加（p < 0.001），而13例MCI受试者中有5例（38%）显示C-（R）-PK 11195摄取增加（11）。11 C-PIB保留增加的MCI亚组也显示皮质（11）C-（R）-PK 11195结合增加（p < 0.036），尽管在多重比较校正后，这种增加仅在额叶皮质中保持显著性。在MCI个体患者中，（11）C-（R）-PK 11195和（11）C-PIB结合的区域水平之间没有相关性：在（11）C-（R）-PK 11195结合增加的5例MCI病例中，仅3例（11）C-PIB保留水平增加。结论：我们的研究结果表明，虽然淀粉样蛋白沉积和小胶质细胞激活可以在体内检测到约50%的轻度认知障碍（MCI）患者，这些病理可以独立发生。MCI患者中小胶质细胞活化的检测表明抗炎治疗可能与AD的预防有关。神经病学（R）2009; 72：56-62
Background: Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (A beta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI). Objective: To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI. Methods: Fourteen subjects with MCI had (11)C-( R)-PK11195 and (11)C-PIB PET with psychometric tests. Results: Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased 11C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding ( p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention. Conclusions: Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD. Neurology (R) 2009; 72: 56-62