Tau Accumulation and Network Breakdown in Alzheimer’s Disease

Hirohisa Watanabe, Epifanio Bagarinao, Takamasa Yokoi, Hiroshi Yamaguchi, Shinsuke Ishigaki, Michihito Mausuda, Masahisa Katsuno, Gen Sobue

研究成果: Chapter

3 被引用数 (Scopus)


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.

ホスト出版物のタイトルAdvances in Experimental Medicine and Biology
出版ステータスPublished - 2019


名前Advances in Experimental Medicine and Biology

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)


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