Suridjan I, Pollock B G, Verhoeff N P L G, Voineskos A N, Chow T, Rusjan P M, Lobaugh N J, Houle S, Mulsant B H, Mizrahi R
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Mol Psychiatry. 2015 Dec;20(12):1579-87. doi: 10.1038/mp.2015.1. Epub 2015 Feb 24.
Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.
我们的主要目的是通过使用正电子发射断层扫描（PET）和18 kDa转运蛋白（TSPO）特异性放射性配体[（18）F]-FEPPA，比较认知功能正常的对照受试者和阿尔茨海默病（AD）患者的神经炎症。对21例AD患者（47 - 81岁）和21例对照受试者（49 - 82岁）在高分辨率研究断层扫描仪上进行了[（18）F]-FEPPA PET扫描。采用具有动脉血浆输入函数的双组织室模型对扫描结果进行分析。比较了以[（18）F]-FEPPA结合为指标的神经炎症差异，并根据TSPO基因（rs6971）的单核苷酸多态性所确定的结合亲和力类别差异进行了调整。在灰质区域，与健康对照受试者相比，AD患者的[（18）F]-FEPPA显著更高。在海马体、前额叶、颞叶、顶叶和枕叶皮质观察到大幅增加（平均Cohen's d = 0.89）。基于体素的分析证实AD患者额叶、颞叶和顶叶皮质存在显著的神经炎症聚集。在白质中，内囊后肢和扣带束的[（18）F]-FEPPA结合升高。顶叶皮质（r = -0.7，P = 0.005）和内囊后肢（r = -0.8，P = 0.001）较高的神经炎症与较差的视觉空间功能相关。此外，内囊后肢较高的[（18）F]-FEPPA结合与语言能力的更大损害相关（r = -0.7，P = 0.004）。通过使用[（18）F]-FEPPA PET可在AD患者全脑的灰质和白质中检测到神经炎症升高。我们的结果还表明神经炎症与一些认知缺陷相关。
