PET of brain amyloid and tau in mild cognitive impairment
PET of brain amyloid and tau in mild cognitive impairment
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DOI：
10.1056/nejmoa054625
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发表时间：
2006-12-21
影响因子：
158.5
通讯作者：
Barrio, Jorge R.
中科院分区：
文献类型：
--
作者：
Small, Gary W.;Kepe, Vladimir;Barrio, Jorge R.
阿尔茨海默病的神经病理学标志是骨髓样老年斑和tau神经元缠结，其在具有轻度认知障碍的阿尔茨海默病风险的人的大脑皮层区域中积累。非侵入性的方法来检测这些异常的蛋白质是潜在的有用的药物发现和diagnostics.METHODSWe招募了83名志愿者与自我报告的记忆问题谁经历了神经和精神评估和正电子发射断层扫描（PET）的替代标记。在认知测试的基础上，25名志愿者被归类为患有阿尔茨海默病，28名为轻度认知障碍，30名为无认知障碍（健康对照）。在注射2-（1-{6-[（2-[F-18]氟乙基）（甲基）氨基]-2-萘基}亚乙基）丙二腈（FDDNP）后进行PET，FDDNP是一种在体外与斑块和缠结结合的分子。所有受试者还接受了2-脱氧-2-[ F-18]氟-D-葡萄糖（FDG）PET，72名受试者接受了磁共振成像（MRI）。（颞叶、顶叶、后扣带回和额叶区域的平均值）在对照组中低于轻度认知障碍组轻度认知功能障碍组的结合值低于阿尔茨海默病组（P <0.001）。FDDNP-PET结合诊断组之间的区别比代谢FDG-PET或体积上MRI.CONCLUSIONSFDDNP-PET扫描可以区分轻度认知功能障碍的人与阿尔茨海默病和那些没有认知功能障碍。该技术作为一种非侵入性方法，可用于确定淀粉样蛋白斑块和tau神经元缠结的局部大脑模式。
BACKGROUNDAmyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics.METHODSWe enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography ( PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment ( healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18] fluoroethyl) ( methyl) amino]-2-naphthyl} ethylidene) malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2- deoxy-2-[ F-18] fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI).RESULTSGlobal values for FDDNP-PET binding ( average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment ( P< 0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease ( P< 0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI.CONCLUSIONSFDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.