Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease
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DOI：
10.1093/brain/aww027
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发表时间：
2016-05-01
期刊：
影响因子：
14.5
通讯作者：
Rabinovici, Gil D.
中科院分区：
文献类型：
--
作者：
Ossenkoppele, Rik;Schonhaut, Daniel R.;Rabinovici, Gil D.
PET示踪剂[F-18]-AV-1451允许对活体受试者的tau病理进行可视化。Ossenkoppele等人。在患有不同阿尔茨海默病变异的患者中使用示踪剂来调查tau沉积的相关性。Tau的病理性聚集，而不是淀粉样β蛋白，与神经退行性变的模式和阿尔茨海默病的临床表现有关。PET示踪剂[F-18]-AV-1451使活体受试者的tau病理可视化。Ossenkoppele等人。在患有不同阿尔茨海默病变异的患者中使用示踪剂来调查tau沉积的相关性。Tau的病理性聚集与神经退行性变的模式和阿尔茨海默病的临床表现有关，而不是淀粉样β蛋白的病理性聚集。正电子发射断层扫描示踪剂F-18-AV1451的出现为可视化活体人脑中tau病理的区域分布提供了独特的机会。在这项研究中，我们测试了tau病理与阿尔茨海默病的症状和葡萄糖低代谢模式密切相关的假设，而淀粉样β蛋白病理的分布更为广泛。我们包括20名符合阿尔茨海默病痴呆或阿尔茨海默病引起的轻度认知障碍的患者，他们表现出各种临床表型，以及15名淀粉样β蛋白阴性的认知正常者，他们接受了F-18-AV1451(Tau)、C-11-PIB(淀粉样β蛋白)和F-18-FDG(葡萄糖代谢)正电子发射断层扫描、载脂蛋白E(APOE)基因分型和神经心理测试。与对照组的体素对比(在P<；0.05家庭错误校正时)显示，后部皮质萎缩患者(阿尔茨海默病的视觉变异型，n=7)的F-18-AV1451和F-18-FDG模式专门针对临床上受影响的大脑后区域，而C-11-PIB广泛结合在整个新皮质。以遗忘症为主的患者(n=5)显示最高的F-18-AV1451在内侧和外侧的颞顶区域。对数遗传性变异型原发进行性失语症(‘语言变异型阿尔茨海默病’，n=5)患者在5名患者中有3名左侧大脑半球F-18-AV1451摄取不对称。在所有三种正电子发射断层扫描的16名阿尔茨海默病患者的30个自由浏览的感兴趣区中，F-18-AV1451和F-18-FDG摄取之间存在强烈的负相关(Pearson‘s r=-0.49+/-0.07，P<；0.001)，而C-11-PIB和F-18-FDG之间的正相关性不那么明显(Pearson’s r=0.16+/-0.09，P<；0.001)和F-18-AV1451和C-11-PIB(皮尔逊相关系数r=0.18+/-0.09，P<；0.001)。以P<；0.05(未校正)为阈值的体素线性回归显示，在所有患者中，年轻与新皮质广泛区域的F-18-AV1451摄取增加相关，而老年与内侧颞叶F-18-AV1451摄取增加相关。ApoE I mu4携带者对F-18-AV1451的颞叶和顶叶摄取均高于非携带者。最后，在特定领域的神经心理测试中表现较差，与F-18-AV1451在关键区域的摄取增加有关，这些区域与记忆(内侧颞叶)、视觉空间功能(枕叶、右侧颞顶皮质)和语言(左侧和右侧颞顶皮质)有关。总之，与淀粉样β蛋白成像相反的是，tau成像显示与阿尔茨海默病的临床和解剖异质性有很强的地区性关联。尽管这些结果是初步的，但这些结果与尸检、动物和脑脊液研究的结果是一致的，并表明tau的病理性聚集与阿尔茨海默病的神经变性模式和临床表现密切相关。
The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.See Sarazin et al. (doi:10.1093/brain/aww041) for a scientific commentary on this article.The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.The advent of the positron emission tomography tracer F-18-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-beta pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-beta-negative cognitively normal individuals, who underwent F-18-AV1451 (tau), C-11-PiB (amyloid-beta) and F-18-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed that F-18-AV1451 and F-18-FDG patterns in patients with posterior cortical atrophy ('visual variant of Alzheimer's disease', n = 7) specifically targeted the clinically affected posterior brain regions, while C-11-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation (n = 5) showed highest F-18-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia ('language variant of Alzheimer's disease', n = 5) demonstrated asymmetric left greater than right hemisphere F-18-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer's disease patients with all three positron emission tomography scans available, there was a strong negative association between F-18-AV1451 and F-18-FDG uptake (Pearson's r = -0.49 +/- 0.07, P < 0.001) and less pronounced positive associations between C-11-PiB and F-18-FDG (Pearson's r = 0.16 +/- 0.09, P < 0.001) and F-18-AV1451 and C-11-PiB (Pearson's r = 0.18 +/- 0.09, P < 0.001). Voxel-wise linear regressions thresholded at P < 0.05 (uncorrected) showed that, across all patients, younger age was associated with greater F-18-AV1451 uptake in wide regions of the neocortex, while older age was associated with increased F-18-AV1451 in the medial temporal lobe. APOE I mu 4 carriers showed greater temporal and parietal F-18-AV1451 uptake than non-carriers. Finally, worse performance on domain-specific neuropsychological tests was associated with greater F-18-AV1451 uptake in key regions implicated in memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging-contrary to amyloid-beta imaging-shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer's disease.Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.