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淀粉样蛋白和tau蛋白正电子发射断层扫描显示正常老年人中存在区域特异性关联。

Amyloid and tau PET demonstrate region-specific associations in normal older people.

作者信息

Lockhart Samuel N, Schöll Michael, Baker Suzanne L, Ayakta Nagehan, Swinnerton Kaitlin N, Bell Rachel K, Mellinger Taylor J, Shah Vyoma D, O'Neil James P, Janabi Mustafa, Jagust William J

机构信息

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA.

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; MedTech West and the Department of Psychiatry and Neurochemistry, University of Gothenburg, 413 45 Gothenburg, Sweden.

出版信息

Neuroimage. 2017 Apr 15;150:191-199. doi: 10.1016/j.neuroimage.2017.02.051. Epub 2017 Feb 21.

Abstract

β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [F]AV-1451 (for tau) and [C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB-AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.

摘要

β-淀粉样蛋白(Aβ)和tau蛋白病理随年龄增长愈发普遍,然而,这两种病理之间的空间关系仍不明确。我们使用[F]AV - 1451(用于检测tau蛋白)和[C]PiB(用于检测Aβ)正电子发射断层扫描(PET)以及1.5T磁共振成像(MRI)图像,研究了46名正常老年人中这两种聚集蛋白之间的局部(同一区域)和非局部(不同区域)关联。虽然局部体素分析显示PiB和AV - 1451示踪剂之间的关联主要在颞叶,但k均值聚类表明,其中一些关联是由示踪剂保留率低的区域驱动的。我们随后进行了全脑逐个区域(局部和非局部)的偏相关分析。我们计算了每个参与者在87个感兴趣区域(ROI)内的平均AV - 1451和PiB摄取值。成对ROI分析显示了许多PiB - AV - 1451的正相关。重要的是,在多个联合皮质区域的PiB与颞叶皮质ROI中的AV - 1451之间发现了强正偏相关(控制年龄、性别和全脑灰质分数,p <.01)。区域PiB与额顶叶AV - 1451摄取之间也存在较少且较弱的正相关。特别是在颞叶ROI中,多个ROI位置的PiB都能强烈预测AV - 1451摄取。这些数据表明,在认知正常的老年人中,Aβ和tau蛋白病理显示出显著的局部和非局部区域关联,整个皮质中PiB摄取增加与颞叶AV - 1451摄取增加相关。Aβ和tau蛋白积累之间的空间关系似乎并不特定于Aβ的位置,这表明无论Aβ在何处积累,颞叶脑区对tau蛋白积累存在区域易损性。

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