In-vivo measurement of activated microglia in dementia
In-vivo measurement of activated microglia in dementia
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DOI：
10.1016/s0140-6736(01)05625-2
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发表时间：
2001-08-11
期刊：
影响因子：
168.9
通讯作者：
Banati, RB
中科院分区：
文献类型：
--
作者：
Cagnin, A;Brooks, DJ;Banati, RB
背景
活化的小胶质细胞在大脑对神经元变性的免疫反应中起关键作用。小胶质细胞从正常的静息状态转变为活化状态与被称为外周苯二氮卓结合位点的受体表达增加有关，这些位点在单核吞噬细胞系的细胞上大量存在。我们利用脑成像研究这些位点在健康个体和阿尔茨海默病患者中的表达。
方法
我们研究了15名正常个体（年龄32 - 80岁）、8名阿尔茨海默病患者和1名轻度认知障碍患者。利用正电子发射断层扫描（PET）和碳 - 11标记的（R）- PK11195（一种外周苯二氮卓结合位点的特异性配体）获得了神经胶质活化的定量体内测量值。
结果
在正常个体中，除了丘脑（发现有年龄相关性增加）外，区域[C - 11]（R）- PK11195结合不随年龄显著变化。相比之下，阿尔茨海默病患者在内嗅皮质、颞顶叶皮质和扣带回皮质中显示区域[C - 11]（R）- PK11195结合显著增加。
解释
在包括轻度和早期形式的阿尔茨海默型痴呆中体内检测到[C - 11]（R）- PK11195结合增加，表明小胶质细胞活化是该疾病发病机制中的一个早期事件。
Background Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease.Methods We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site.Findings In normal individuals, regional [C-11](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [C-11](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex.Interpretation In-vivo detection of increased [C-11](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.