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