Tau Accumulation and Network Breakdown in Alzheimer’s Disease
Tau Accumulation and Network Breakdown in Alzheimer’s Disease
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阿尔茨海默病中的 Tau 蛋白积累和网络崩溃
DOI：
10.1007/978-981-32-9358-8_19
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sobue Gen
中科院分区：
文献类型：
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作者：
Watanabe Hirohisa;Bagarinao Epifanio;Yokoi Takamasa;Yamaguchi Hiroshi;Ishigaki Shinsuke;Mausuda Michihito;Katsuno Masahisa;Sobue Gen
错折叠和聚集的tau蛋白和淀粉样蛋白β（Aβ）是阿尔茨海默病（AD）的病理标志。这些异常蛋白质失去了它们的生理作用，获得神经毒性，并在神经系统中传播。尽管对分子病理生理学的理解不断加深，但分子改变、病理变化与痴呆发作和进展之间的关系仍有待阐明。连通性是大脑的独有特征，功能和解剖网络的完整性和分离对于正常功能至关重要。有趣的是，许多磁共振成像（MRI）研究表明，大脑区域之间连续的结构和功能断开支持AD是一种断开综合征的想法。最近的几项研究使用先进的Aβ和tau PET示踪剂的组合，通过数据驱动的统计方法，静息态功能MRI和扩散张量成像，揭示了tau保留的空间分布模式以及AD中tau保留与功能/结构网络破坏之间的关系。tau PET痕迹的区域保留与灰质变化、结构网络破坏和认知功能测试相关。tau蛋白保留将主要沿着与认知相关的静息状态网络传播，并且在网络枢纽中更常见，这些网络枢纽表现出与网络内以及没有网络的其他区域的许多强互连。主要是楔前叶和扣带回后部常被累及，可能是与正常认知状态下临床表现的痴呆相关的关键节点。
Misfolded and aggregated tau and amyloid β (Aβ) proteins are the pathological hallmarks of Alzheimer’s disease (AD). These aberrant proteins lose their physiological roles, acquire neurotoxicity, and propagate across neural systems. Despite the growing understanding of the molecular pathophysiology, the relationship among molecular alterations, pathological changes, and dementia onset and progression remain to be elucidated. Connectivity is an exclusive characteristic of the brain, and the integrity and segregation of the functional and anatomical networks are crucial for normal functioning. Interestingly, a lot of magnetic resonance imaging (MRI) studies have demonstrated successive structural and functional disconnection among brain regions supporting the idea that AD is a disconnection syndrome. Recent several studies using the combination of cutting-edge Aβ and tau PET tracers integrated by data-driven statistical methods, resting-state functional MRI, and diffusion tensor imaging have shed light on the spatial distribution pattern of tau retention as well the relationship between tau retention and functional/structural network disruption in AD. Regional retention of tau PET traces is associated with gray matter changes, structural network disruption, and cognitive function tests. The tau retention will mainly spread along with cognition-related resting state networks and be more common in the network hubs which exhibit many strong interconnections with other regions within the network as well as without the networks. Mainly, precuneus and posterior cingulate gyrus are commonly involved and can be the critical nodes associated with clinically manifested dementia from the normal cognitive state.