異常型タウの構造多型は多様なタウオパチー病理の形成に寄与する

Role of Structural Polymorphisms of Tau Filaments in the Pathological Diversity of Tauopathies

タウオパチー患者脳内に蓄積するアミロイド様線維に構造変化したタウは，神経細胞およびグリア細胞内で疾患を特徴付ける病理構造物を形成する。患者脳から抽出した異常型タウの構造学的・生化学的分類は，その構造多型の存在を裏付ける。またプリオン様伝播実験モデルにおいて疾患特徴的なタウ凝集および線維形成が再現されることは，異常型タウの呈する高次構造が多様なタウオパチー病理を決定づける因子であることを示唆する。

Abstract

Pathological tau protein accumulated in the brain of patients with tauopathies undergoes structural changes into amyloid-like filaments and forms the intracellular deposits that characterize the disease. Structural and biochemical classification of pathogenic tau extracted from patients' brains supports the hypothesis that structural polymorphisms of tau filaments occur in the brain. Additionally, disease-specific tau pathologies are recapitulated in in vitro and in vivo experimental models that mimic tau aggregation and dissemination and indicate that conformation of tau filaments is a key contributor to the pathological diversity in tauopathy. In this review, we describe the structural and biochemical features of pathological tau extracted from the brain of patients with tauopathies and discuss the possible mechanisms underlying amplification and dissemination of pathological tau in the brain.