Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.
Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.
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DOI：
10.1186/s13024-021-00448-1
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发表时间：
2021-04-26
影响因子：
15.1
通讯作者：
Rosa-Neto P
中科院分区：
文献类型：
--
作者：
Terada T;Therriault J;Kang MSP;Savard M;Pascoal TA;Lussier F;Tissot C;Wang YT;Benedet A;Matsudaira T;Bunai T;Obi T;Tsukada H;Ouchi Y;Rosa-Neto P
线粒体电子传递链异常已报道在阿尔茨海默病（AD）死后病理标本。然而，目前尚不清楚淀粉样蛋白和tau蛋白如何与体内线粒体功能障碍相关。本研究的目的是利用新型线粒体复合物I PET显像剂[18F]BCPP-EF，评估轻度AD患者线粒体功能障碍与AD病理生理之间的局部关系。32例淀粉样蛋白和tau阳性的轻度AD痴呆患者（平均年龄±SD: 71.1±8.3岁）接受了一系列PET测量，检测[18F]BCPP-EF线粒体功能，[11C]PBB3检测tau沉积，[11C] PiB检测淀粉样蛋白沉积。还招募了年龄匹配的正常对照受试者。进行了线粒体复合体I活性、淀粉样蛋白和tau沉积水平的主体间和主体内比较。[18F]内侧颞区BCPP-EF摄取明显较低，突出了线粒体参与AD病理的重要性。[11] AD患者颞顶区PBB3摄取更大。brak期I-II区感兴趣区分析显示[18F]BCPP-EF SUVR与[11C]PBB3 BPND呈显著负相关（R = 0.2679, p = 0.04）， [11C] PiB SUVR无显著负相关。我们的研究结果表明，线粒体复合体I与[11C]PBB3评估的tau负荷密切相关，PBB3可能在其脱靶结合的存在下受到影响。线粒体复合体I功能障碍与淀粉样蛋白负荷之间没有关联，这表明线粒体功能障碍在反内嗅区和内嗅区是轻度AD大脑中神经元损伤的反映。在线版本包含补充材料，可在10.1186/s13024-021-00448-1获得。
Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD. The online version contains supplementary material available at 10.1186/s13024-021-00448-1.