KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

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 】

Career 【 Display / hide 】

• 2004.04

  -

  2006.03

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

• 2006.04

  -

  2008.08

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

• 2008.09

  -

  2014.12

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

• 2015.01

  -

  2016.11

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

• 2016.12

  -

  Present

  Keio University, School of Medicine, Physiology Department, Instructor

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2001.04

  -

  2003.03

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

  University, Graduated, Master's course

• 2003.04

  -

  2006.03

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

  University, Graduated, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

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

  顆粒状凝集体を介したタウ線維形成：タウ線維中間体の同定

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Molecular biology

• Life Science / Neuroscience-general

• Life Science / Anatomy and histopathology of nervous system

• Life Science / Pathological biochemistry

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• iPS cells

• Epilepsy

• Epilepsy

• Alzheimer's disease

• Tau protein

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Papers 【 Display / hide 】

Papers 【 Display / hide 】

• 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.

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

• 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

  • Access to Document (DOI)

• 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

  • Access to Document (DOI)

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

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

• The expression analysis of Tau protein in hiPSC-derived neurons or directly converted neurons from fibroblasts

  Maeda, Sumihiro

  科学研究費補助金研究成果報告書 2018

Reviews, Commentaries, etc. 【 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

  Article, review, commentary, editorial, etc. (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

  Article, review, commentary, editorial, etc. (scientific journal), Joint Work

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

  MAEDA Sumihiro

  Alzheimer's association  2004

  Article, review, commentary, editorial, etc. (scientific journal), Joint Work

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Epileptic activity caused by soluble tau species

  MAEDA Sumihiro

  タウ研究会2017, 

  2017.08

  , 

  Symposium, workshop panel (public), 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 lecture, seminar, tutorial, course, or other speech

• 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 presentation

• タウオリゴマー

  MAEDA Sumihiro

  日本認知症学会　学術集会, 

  2015

  , 

  Symposium, workshop panel (public)

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

  MAEDA Sumihiro

  2015

  , 

  Public lecture, seminar, tutorial, course, or other speech

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

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

• 尿由来細胞を用いた神経疾患モデル細胞の作成

  2021.04

  -

  2025.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

• 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

  2017.04

  -

  2019.03

  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

  2007.04

  -

  2009.03

  文部科学省, Grant-in-Aid for Scientific Research, Akihiko Takashima, Coinvestigator(s)

• タウ凝集阻害剤の検索と評価

  2007.04

  -

  2008.08

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

Awards 【 Display / hide 】

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 Taught 【 Display / hide 】

• PHYSIOLOGY OF HUMAN BODY

  2023

• PHYSIOLOGY 2

  2023

• PHYSIOLOGY OF HUMAN BODY

  2022

• PHYSIOLOGY 2

  2022

• PHYSIOLOGY 2

  2021

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 再生・遺伝子の科学

  Keio University

  2017.04

  -

  2018.03

  , 

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

  Alzheimer's disease, Tau protein

• 尿生成

  Keio University

  2017.04

  -

  2018.03

  , 

  Autumn Semester, Laboratory work/practical work/exercise, Outside own faculty (within Keio), 120people

• 自主学習プログラム

  Keio University

  2017.04

  -

  2018.03

  , 

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

Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本神経科学会, 

  2016

  -

  Present

• Society for Neuroscience, 

  2004

  -

  Present

• 日本認知症学会, 

  2003

  -

  Present