Maeda, Sumihiro



School of Medicine, Department of Physiology (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

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Profile 【 Display / hide

  • In 2001, I joined the laboratory for Alzheimer’s disease (AD) at RIKEN Institute and started my PhD works on tau protein. During my doctoral thesis, I found an oligomeric species of tau aggregate in in vitro and purified tau oligomers from AD brain, which was the first purification of oligomeric species from human brains. After I finished my doctoral thesis in 2006, I obtained a post-doc position in the same laboratory to translate my findings into therapies. To find therapeutic targets, we searched two kinds of molecules: (1) aggregation inhibitors to disrupt the aggregation of tau and (2) probes for tau oligomer to use for diagnosis before the onset of AD. In 2008 I joined the laboratory of Dr. Lennart Mucke at the Gladstone Institute of Neurological Disease. I studied the pathogenesis of A152T human tau variant (hTau-A152T) that is genetically linked to AD for the first time and found that hTau-A152T could induce epileptic activity independent of tau aggregation. In 2016, I was appointed instructor at Keio university school of medicine and launched some projects to study the pathogenesis of tau protein using iPSC-derived neurons.

Career 【 Display / hide

  • 2004.04

    RIKEN, Brain Science Institute, Laboratory for Alzheimer's Disease, Junior research associate

  • 2006.04

    RIKEN, Brain Science Institute, Laboratory for Alzheimer's Disease, Post-doctoral fellow

  • 2008.09

    The J. David Gladstone Institutes, Gladstone Institute of Neurological Disease, Post-doctoral fellow

  • 2015.01

    The J. David Gladstone Institutes, Gladstone Institute of Neurological Disease, Research scientist

  • 2016.12

    Keio University, School of Medicine, Physiology Department, Instructor

Academic Background 【 Display / hide

  • 2001.04

    Tokyo Institute of Technology, Department of Life Science and Technology, 分子生命科学専攻

    Japan, University, Graduated, Master's course

  • 2003.04

    Tokyo Institute of Technology, Department of Life Science and Technology, 分子生命科学専攻

    Japan, University, Graduated, Doctoral course

Academic Degrees 【 Display / hide

  • Ph. D., Tokyo Institute of Technology, 2006.03



Research Areas 【 Display / hide

  • Neurophysiology / General neuroscience

  • Nerve anatomy/Neuropathology

  • Molecular biology

  • Molecular biology

  • Pathological medical chemistry

Research Keywords 【 Display / hide

  • iPS cells

  • Epilepsy

  • Epilepsy

  • Alzheimer's disease

  • Tau protein

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Papers 【 Display / hide

  • Neuronal levels and sequence of tau modulate the power of brain rhythms

    Das M., Maeda S., Hu B., Yu G., Guo W., Lopez I., Yu X., Tai C., Wang X., Mucke L.

    Neurobiology of Disease (Neurobiology of Disease)  117   181 - 188 2018.09

    ISSN  09699961

     View Summary

    © 2018 Elsevier Inc. Neural network dysfunction may contribute to functional decline and disease progression in neurodegenerative disorders. Diverse lines of evidence suggest that neuronal accumulation of tau promotes network dysfunction and cognitive decline. The A152T-variant of human tau (hTau-A152T) increases the risk of Alzheimer's disease (AD) and several other tauopathies. When overexpressed in neurons of transgenic mice, it causes age-dependent neuronal loss and cognitive decline, as well as non-convulsive epileptic activity, which is also seen in patients with AD. Using intracranial EEG recordings with electrodes implanted over the parietal cortex, we demonstrate that hTau-A152T increases the power of brain oscillations in the 0.5–6 Hz range more than wildtype human tau in transgenic lines with comparable levels of human tau protein in brain, and that genetic ablation of endogenous tau in Mapt−/− mice decreases the power of these oscillations as compared to wildtype controls. Suppression of hTau-A152T production in doxycycline-regulatable transgenic mice reversed their abnormal network activity. Treatment of hTau-A152T mice with the antiepileptic drug levetiracetam also rapidly and persistently reversed their brain dysrhythmia and network hypersynchrony. These findings suggest that both the level and the sequence of tau modulate the power of specific brain oscillations. The potential of EEG spectral changes as a biomarker deserves to be explored in clinical trials of tau-lowering therapeutics. Our results also suggest that levetiracetam treatment is able to counteract tau-dependent neural network dysfunction. Tau reduction and levetiracetam treatment may be of benefit in AD and other conditions associated with brain dysrhythmias and network hypersynchrony.

  • Frontotemporal dementia with Parkinsonism linked to chromosome-17 mutations enhance tau oligomer formation

    Maeda S., Sato Y., Takashima A.

    Neurobiology of Aging (Neurobiology of Aging)  69   26 - 32 2018.09

    ISSN  01974580

     View Summary

    © 2018 Elsevier Inc. The P301 L mutation in tau, a microtubule-associated protein, causes frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17) that is accompanied by formation of filamentous polymers of tau. The mutation reduces the binding capability of microtubules and enhances tau filament formation. However, it is unclear whether the P301 L mutation increases the formation of the intermediates of tau filaments that are suggested to be a toxic species of tau. To determine the amount and structure of the intermediates harboring with the P301L mutation, we purified recombinant versions of wild-type, P301L, and 4 other mutants (i.e., P301S, P301T, V337M, and R406W) tau proteins and analyzed the heparin-induced aggregation of those tau constructs. We found that all of the FTDP-17 mutants increased levels of the intermediate tau oligomers. The sizes were determined by atomic force microscopy and laser light scattering. The V337M and R406W oligomers were similar in size to the wild-type, but the P301L, P301T, and P301S mutants formed smaller oligomers. In a P301L transgenic mouse model, we found tau aggregates that were similar in size to the recombinant tau oligomer. These results indicate that FTDP-17 mutations contribute to the pathogenesis via the increased formation of tau oligomers.

  • Tau Phosphorylation-Much More than a Biomarker

    Maeda, Sumihiro, Mucke, Lennart

    NEURON 92 ( 2 ) 265 - 267 2016.10

    Research paper (scientific journal),  ISSN  0896-6273

  • Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice

    Maeda, Sumihiro, Djukic, Biljana, Taneja, Praveen, Yu, Gui-Qiu, Lo, Iris, Davis, Allyson, Craft, Ryan, Guo, Weikun, Wang, Xin, Kim, Daniel, Ponnusamy, Ravikumar, Gill, T. Michael, Masliah, Eliezer, Mucke, Lennart

    EMBO REPORTS 17 ( 4 ) 530 - 551 2016.04

    Research paper (scientific journal),  ISSN  1469-221X

  • Toxic tau oligomer formation blocked by capping of cysteine residues with 1,2-dihydroxybenzene groups

    Soeda, Yoshiyuki, Yoshikawa, Misato, Almeida, Osborne F. X., Sumioka, Akio, Maeda, Sumihiro, Osada, Hiroyuki, Kondoh, Yasumitsu, Saito, Akiko, Miyasaka, Tomohiro, Kimura, Tetsuya, Suzuki, Masaaki, Koyama, Hiroko, Yoshiike, Yuji, Sugimoto, Hachiro, Ihara, Yasuo, Takashima, Akihiko

    NATURE COMMUNICATIONS 6   530 - 551 2015.12

    Research paper (scientific journal),  ISSN  2041-1723

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Tau oligomerization: a role for tau aggregation intermediates linked to neurodegeneration.

    MAEDA Sumihiro

    Curr Alzheimer Res 5 ( 6 ) 591 - 598 2008

    Introduction and explanation (scientific journal), Joint Work

  • 神経原線維変化形成機構

    MAEDA Sumihiro

    Dementia Japan (日本認知症学会)  20 ( 3 ) 262 - 270 2006.12

    Introduction and explanation (scientific journal), Joint Work

  • Mechanism of Neurofibrillary Tangle Formation: Tau Accumulation and Fibril Formation

    MAEDA Sumihiro

    Alzheimer's association  2004

    Introduction and explanation (scientific journal), Joint Work

Presentations 【 Display / hide

  • Epileptic activity caused by soluble tau species

    MAEDA Sumihiro

    タウ研究会2017, 2017.08, Symposium, Workshop, Panelist (public offering), タウ研究会 運営委員会

  • Aggregation-dependent and –independent pathogenesis of tau protein

    MAEDA Sumihiro

    Summer school for 2017, 2017, Public discourse, seminar, tutorial, course, lecture and others

  • Analysis of network dysfunction in hTau-A152T transgenic mice identifies potential new biomarker and opportunity for therapeutic intervention

    MAEDA Sumihiro

    Society for Neuroscience annual meeting, 2016, Poster (general)

  • タウオリゴマー

    MAEDA Sumihiro

    日本認知症学会 学術集会, 2015, Symposium, Workshop, Panelist (public offering)

  • Behavioral, Synaptic, and Neuropathological Changes Caused by A152T Human Tau without Mature Tau Aggregates

    MAEDA Sumihiro

    2015, Public discourse, seminar, tutorial, course, lecture and others

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • ヒトiPS、線維芽細胞から直接誘導された神経細細胞におけるタウタンパク質の解析


    文部科学省, Grant-in-Aid for Scientific Research, Sumihiro Maeda, Research grant, Principal Investigator

  • 神経原線維変化形成機構


    文部科学省, Grant-in-Aid for Scientific Research, Akihiko Takashima, Co-investigator

  • タウ凝集阻害剤の検索と評価


    MEXT, Grant-in-Aid for Scientific Research, Sumihiro Maeda, Research grant, Principal Investigator

Awards 【 Display / hide

  • Career advancement award

    2014, The J. David Gladstone Institute

  • Poster presentation award (1st)

    2013, The J. David Gladstone Institute

  • Scientific leadership award

    2012, The J. David Gladstone Institute

     View Description

    This award is given to researchers (basically one researcher, rarely two researchers) who showed excellent readership during their research activities.

  • Poster presentation award (3rd)

    2012, The J. David Gladstone Institute

  • Excellent paper award

    2006, Neuroscience Research

     View Description

    One of the three papers selected as excellent papers among the papers published on Neuroscience Research.


Courses Taught 【 Display / hide



Courses Previously Taught 【 Display / hide

  • 再生・遺伝子の科学

    Keio University, 2017, Autumn Semester, Other, Lecture, Lecturer outside of Keio, 40people

    Alzheimer's disease, Tau protein

  • 尿生成

    Keio University, 2017, Autumn Semester, General education subject, Laboratory work/practical work/exercise, Outside own faculty (within Keio), 120people

  • 自主学習プログラム

    Keio University, 2017, Spring Semester, Other, Laboratory work/practical work/exercise, 10h, 2people