Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA.
Brain. 2013 Jul;136(Pt 7):2228-38. doi: 10.1093/brain/awt145. Epub 2013 Jun 17.
Neuroinflammation is a pathological hallmark of Alzheimer's disease, but its role in cognitive impairment and its course of development during the disease are largely unknown. To address these unknowns, we used positron emission tomography with (11)C-PBR28 to measure translocator protein 18 kDa (TSPO), a putative biomarker for inflammation. Patients with Alzheimer's disease, patients with mild cognitive impairment and older control subjects were also scanned with (11)C-Pittsburgh Compound B to measure amyloid burden. Twenty-nine amyloid-positive patients (19 Alzheimer's, 10 mild cognitive impairment) and 13 amyloid-negative control subjects were studied. The primary goal of this study was to determine whether TSPO binding is elevated in patients with Alzheimer's disease, and the secondary goal was to determine whether TSPO binding correlates with neuropsychological measures, grey matter volume, (11)C-Pittsburgh Compound B binding, or age of onset. Patients with Alzheimer's disease, but not those with mild cognitive impairment, had greater (11)C-PBR28 binding in cortical brain regions than controls. The largest differences were seen in the parietal and temporal cortices, with no difference in subcortical regions or cerebellum. (11)C-PBR28 binding inversely correlated with performance on Folstein Mini-Mental State Examination, Clinical Dementia Rating Scale Sum of Boxes, Logical Memory Immediate (Wechsler Memory Scale Third Edition), Trail Making part B and Block Design (Wechsler Adult Intelligence Scale Third Edition) tasks, with the largest correlations observed in the inferior parietal lobule. (11)C-PBR28 binding also inversely correlated with grey matter volume. Early-onset (<65 years) patients had greater (11)C-PBR28 binding than late-onset patients, and in parietal cortex and striatum (11)C-PBR28 binding correlated with lower age of onset. Partial volume corrected and uncorrected results were generally in agreement; however, the correlation between (11)C-PBR28 and (11)C-Pittsburgh Compound B binding was seen only after partial volume correction. The results suggest that neuroinflammation, indicated by increased (11)C-PBR28 binding to TSPO, occurs after conversion of mild cognitive impairment to Alzheimer's disease and worsens with disease progression. Greater inflammation may contribute to the precipitous disease course typically seen in early-onset patients. (11)C-PBR28 may be useful in longitudinal studies to mark the conversion from mild cognitive impairment or to assess response to experimental treatments of Alzheimer's disease.
神经炎症是阿尔茨海默病的病理标志，但它在认知障碍中的作用及其在疾病发展过程中的变化尚不清楚。为了解决这些未知问题，我们使用正电子发射断层扫描技术（PET）结合（11）C-PBR28 来测量转位蛋白 18 kDa（TSPO），这是一种炎症的潜在生物标志物。我们还对阿尔茨海默病患者、轻度认知障碍患者和老年对照组进行了（11）C-Pittsburgh Compound B 扫描，以测量淀粉样蛋白负荷。共有 29 名淀粉样蛋白阳性患者（19 名阿尔茨海默病患者，10 名轻度认知障碍患者）和 13 名淀粉样蛋白阴性对照组患者参与了本研究。本研究的主要目的是确定 TSPO 结合是否在阿尔茨海默病患者中升高，次要目的是确定 TSPO 结合是否与神经心理学测量、灰质体积、（11）C-Pittsburgh Compound B 结合或发病年龄相关。与对照组相比，阿尔茨海默病患者而非轻度认知障碍患者的皮质脑区（11）C-PBR28 结合更高。最大的差异出现在顶叶和颞叶，而皮质下区域和小脑没有差异。（11）C-PBR28 结合与简易精神状态检查（Folstein Mini-Mental State Examination）、临床痴呆评定量表总和框（Clinical Dementia Rating Scale Sum of Boxes）、逻辑记忆即时（韦氏记忆量表第三版）（Logical Memory Immediate）、连线测验 B 部分和积木设计（韦氏成人智力量表第三版）（Trail Making part B and Block Design）任务的表现呈负相关，在顶下小叶观察到最大的相关性。（11）C-PBR28 结合也与灰质体积呈负相关。发病年龄早（<65 岁）的患者比发病年龄晚的患者（11）C-PBR28 结合更高，并且在顶叶皮质和纹状体中，（11）C-PBR28 结合与发病年龄呈负相关。部分容积校正和未校正的结果基本一致；然而，（11）C-PBR28 与（11）C-Pittsburgh Compound B 结合的相关性仅在部分容积校正后才出现。结果表明，神经炎症，由 TSPO 增加（11）C-PBR28 结合所指示，发生在轻度认知障碍转化为阿尔茨海默病之后，并随着疾病的进展而恶化。更大的炎症可能导致早发性患者通常出现的急剧疾病进程。（11）C-PBR28 可能在纵向研究中用于标记从轻度认知障碍的转化，或用于评估阿尔茨海默病的实验治疗反应。
