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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

マウス脳における内在性および外来性 tau の局在
Distribution of endogenous and exogenous tau in the mouse brain

  • P2-288
  • 久保 厚子 / Atsuko Kubo:1 御園生 裕明 / Hiroaki Misono:2 松山 誠 / Makoto Matsuyama:4 高島 明彦 / Akihiko Takashima:5 井原 康夫 / Yasuo Ihara:1,3 宮坂 知宏 / Tomohiro Miyasaka:1 
  • 1:同志社大学 生命医科学部 神経病理学 / Dept of Neuropathology, Faculty of Life and Medical Sciences, Doshisha Univ 2:同志社大学大学院 脳科学研究科 チャネル病態生理部門 / Lab for Ion Channel Pathophysiology, Graduate School of Brain Science, Doshisha Univ 3:同志社大学大学院 脳科学研究科 認知記憶加齢部門 / Lab for Cognition, Memory and Aging, Graduate School of Brain Science, Doshisha Univ 4:重井医学研究所 分子遺伝部門 / Division of Molecular Genetics, Shigei Medical Research Institute 5:独立行政法人国立長寿医療研究センター 認知症先進医療開発センター / Dept of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for  

Tau, a microtubule-associated protein, is the major component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) and related tauopathies. In normal neurons, tau binds to and stabilizes axonal microtubules. In AD, tau becomes hyperphosphorylated, missorted into dendrites and neuronal somata, and then form NFTs. Abnormally deposited tau such as NFTs has been extensively studied by conventional pathological techniques, but we do not know why endogenous tau localizes on axonal microtubules, although they are abundantly expressed in neurons. In order to investigate distinct distribution of tau, we developed the immunocytochemical technique, which can visualize the physiological tau in the brain tissues. First, we have examined the distribution of endogenous tau in the hippocampus of wild-type mouse. Tau is exclusively found in the axonal compartment but barely in dendrites or neuronal cell bodies. Tau is distributed as punctate along axonal microtubules. Endogenous tau is clustered in presumably presynaptic portions but never found in dendritic spines. Next, we compared the distribution of endogenous and exogenous tau in the brains of tau-transgenic (tau-Tg) mice that develop tau-pathology resembling human tauopathy and tau-knock-in (tau-KI) mice that have never led to tauopathy. In tau-Tg mice, exogenous tau localizes in dendrites and cell somata in contrast to endogenous tau. This is conserved throughout the developmental stage indicating that exogenous tau is missorted as early as in the presymptomatic stage. Unexpectedly, exogenous tau in KI mice has the normal distribution. This suggests that the dysfunction of tau-sorting machinery is involved in the NFT formation.

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