Tau Pathology Distribution in Alzheimer's disease Corresponds Differentially to Cognition-Relevant Functional Brain Networks.
Tau Pathology Distribution in Alzheimer's disease Corresponds Differentially to Cognition-Relevant Functional Brain Networks.
复制标题
DOI：
10.3389/fnins.2017.00167
复制
发表时间：
2017
影响因子：
4.3
通讯作者：
Schöll M
中科院分区：
文献类型：
--
作者：
Hansson O;Grothe MJ;Strandberg TO;Ohlsson T;Hägerström D;Jögi J;Smith R;Schöll M
神经病理学研究表明，阿尔茨海默病（AD）中过度磷酸化tau蛋白的典型神经病理学病变优先影响特定脑区，而其他脑区相对较少。已经表明，AD中tau病理学的不同区域分布概况可能是人脑固有网络结构的结果。因此，受tau病理学传播影响最大的空间分布的大脑区域可能反映了相互连接的神经元系统。在这里，我们使用18F-AV 1451 tau敏感的正电子发射断层扫描（PET）成像表征了AD中tau病理的全脑区域分布概况，并研究了这种模式与人脑功能网络组织的关系。具体来说，我们量化了PET证实的tau病理学在AD中的区域分布模式与健康受试者的大规模静息状态功能磁共振成像（rs-fMRI）数据所表征的功能性脑网络的空间对应关系。在前驱和显性AD病例的两个独立样本中表征了与对照相比AD中PET证实的tau病理学增加的区域分布模式（Swedish BioFINDER研究，n = 44; ADNI研究，n = 35）。在BioFINDER研究中，我们发现典型的AD tau模式主要涉及颞叶皮层的下、内侧和外侧区域，以及楔前叶/后扣带回和顶叶和枕叶皮层的外侧部分。这种模式主要与背侧注意重叠，并在一定程度上与高级视觉、边缘系统和部分默认模式网络重叠。在ADNI复制样本中，PET证实的tau病理学（代表AD病例的前驱组）不太明显，但显示出高度相似的空间分布特征，表明持续进展的区域模式的早期快照。总之，本研究表明，AD中tau聚集体的区域沉积主要影响初级感觉运动网络的高阶认知，但似乎并不特异于默认模式或相关边缘系统网络。
Neuropathological studies have shown that the typical neurofibrillary pathology of hyperphosphorylated tau protein in Alzheimer's disease (AD) preferentially affects specific brain regions whereas others remain relatively spared. It has been suggested that the distinct regional distribution profile of tau pathology in AD may be a consequence of the intrinsic network structure of the human brain. The spatially distributed brain regions that are most affected by the spread of tau pathology may hence reflect an interconnected neuronal system. Here, we characterized the brain-wide regional distribution profile of tau pathology in AD using 18F-AV 1451 tau-sensitive positron emission tomography (PET) imaging, and studied this pattern in relation to the functional network organization of the human brain. Specifically, we quantified the spatial correspondence of the regional distribution pattern of PET-evidenced tau pathology in AD with functional brain networks characterized by large-scale resting state functional magnetic resonance imaging (rs-fMRI) data in healthy subjects. Regional distribution patterns of increased PET-evidenced tau pathology in AD compared to controls were characterized in two independent samples of prodromal and manifest AD cases (the Swedish BioFINDER study, n = 44; the ADNI study, n = 35). In the BioFINDER study we found that the typical AD tau pattern involved predominantly inferior, medial, and lateral temporal cortical areas, as well as the precuneus/posterior cingulate, and lateral parts of the parietal and occipital cortex. This pattern overlapped primarily with the dorsal attention, and to some extent with higher visual, limbic and parts of the default-mode network. PET-evidenced tau pathology in the ADNI replication sample, which represented a more prodromal group of AD cases, was less pronounced but showed a highly similar spatial distribution profile, suggesting an earlier-stage snapshot of a consistently progressing regional pattern. In conclusion, the present study indicates that the regional deposition of tau aggregates in AD predominantly affects higher-order cognitive over primary sensory-motor networks, but does not appear to be specific for the default-mode or related limbic networks.