Tsuneya Ikezu, M.D., Ph.D.

Professor, Department of Neuroscience and Director, Molecular NeuroTherapeutics Laboratory, Mayo Clinic Florida

Dr. Tsuneya Ikezu is a Professor in the Department of Neuroscience and Director, Molecular NeuroTherapeutics Laboratory at the Mayo Clinic in Florida.  Research in the clinic focuses on neuroimmune cell-mediated regulations of neuronal function, neurogenesis, neuroinflammation, and neurodegeneration. Researchers in Dr. Ikezu’s lab are particularly interested in how the innate immune-related cells, extracellular vehicles (EVs), and molecules in the central nervous system (CNS) influence the pathology and progression of select neurodegenerative disorders such as Alzheimer’s disease (AD) and frontotemporal dementia.

Prior to this, Dr. Ikezu was Professor of Pharmacology and Neurology at Boston University School of Medicine and led the Laboratory of Molecular NeuroTherapeutics for over 10 years. He has been investigating Alzheimer’s disease (AD) for over 20 years, and he has performed pioneering research into how modulation of neuroinflammation or neurogenesis enhances hippocampal function and ameliorates AD-like neuropathology through viral gene transfer system. He originally discovered caveolae as a platform of APP processing, cloned tau-tubulin kinase-1 as a neuron-specific tau kinase, characterized anti-inflammatory cytokine modulation of hippocampal neurogenesis and cognitive enhancement, microglia-neural stem cell interactions, and recently discovered new roles of microglia and exosomes for spreading of pathogenic tau protein in the brain.

He has authored more than 99 journal articles, edited the textbook Neuroimmune Pharmacology (Springer Nature) and served on several editorial boards. Over his career, Dr. Ikezu has received Vada Kinman Oldfield Alzheimer’s Research Award (2000), Inge Grundke Iqbal Award from Alzheimer’s Association (2016) and recently Jack Spivack Excellence in Neuroscience Award (2018).

Dr. Ikezu received his M.D. and Ph.D. from University of Tokyo School of Medicine, completed post-doctoral trainings at Massachusetts General Hospital and Cleveland Clinic Foundation, and was Professor of Pharmacology and Experimental Neuroscience at University of Nebraska Medical Center prior to joining Boston University (1999-2010).

Follow Dr. Ikezu at https://www.tsuneyaikezu.com and on Twitter at https://twitter.com/TsuneyaIkezu

Dr. Ikezu’s lab webpage: The Molecular Neurotherapeutics Laboratory at Mayo Clinic 

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Muraoka, S., DeLeo, A. M., Sethi, M. K., Yukawa-Takamatsu, K., Yang, Z., Ko, J., Hogan, J. D., Ruan, Z., You, Y., Wang, Y., Medalla, M., Ikezu, S., Chen, M., Xia, W., Gorantla, S., Gendelman, H. E., Issadore, D., Zaia, J., & Ikezu, T. Proteomic and biological profiling of extracellular vesicles from Alzheimer’s disease human brain tissues, Alzheimer's & Dementia, April 17, 2020, Read More

Muraoka, S., Lin, W., Chen, M., Hersh, S. W., Emili, A., Xia, W., & Ikezu, T. Assessment of separation methods for extracellular vesicles from human and mouse brain tissues and human cerebrospinal fluids, Methods, February 5, 2020, Read More

Jun, G. R., You, Y., Zhu, C., Meng, G., Chung, J., Panitch, R., Hu, J., Xia, W., Alzheimer's Disease Genetics Consortium, Bennett, D. A., Foroud, T. M., Wang, L. S., Haines, J. L., Mayeux, R., Pericak-Vance, M. A., Schellenberg, G. D., Au, R., Lunetta, K. L., Ikezu, T., Stein, T. D., … Farrer, L. A. Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer’s disease., Alzheimer's & Dementia, February 9, 2022, Read More

Clayton, K., Delpech, J. C., Herron, S., Iwahara, N., Ericsson, M., Saito, T., Saido, T. C., Ikezu, S., & Ikezu, T. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model, Molecular Neurodegeneration, March 22, 2021, Read More

Yukawa, K., Yamamoto-Mcguire, S., Cafaro, L., Hong, C., Kamme, F., Ikezu, T., & Ikezu, S. Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice, Acta Neuropathologica Communications, October 19, 2023, Read More

Yin, Z., Rosenzweig, N., … Ikezu, T., … Tanzi, R., E., … Holtzman, D., M., & Butovsky, O. APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints, Nature Immunology, September 25, 2023, Read More

Liu, C. C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A. C., Rosenberg, C. L., Doss, S. V., Zhao, J., Wren, M. C., Jia, L., Ren, Y., Ikezu, T. C., Lu, W., Fu, Y., Caulfield, T., Trottier, Z.A., Knight, J., Chen, Y., Linares, C., Wang, X., Kurti, A., Asmann, Y.W., Wszolek, Z.K., Smith, G.E., Vemuri, P., Kantarci, K., Knopman, D.S., Lowe, V.J., Jack, C.R. Jr, Parisi, J.E., Ferman, T.J., Boeve, B.F., Graff-Radford, N.R., Petersen, R.C., Younkin, S.G., Fryer, J.D., Wang, H., Han, X., Frieden, C., Dickson, D.W., Ross, O.A., Bu, G. APOE3-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia, Science Translational Medicine, September 29, 2021, Read More

Apicco, D. J., Ash, P. E. A., Maziuk, B., LeBlang, C., Medalla, M., Al Abdullatif, A., Ferragud, A., Botelho, E., Ballance, H. I., Dhawan, U., Boudeau, S., Cruz, A. L., Kashy, D., Wong, A., Goldberg, L. R., Yazdani, N., Zhang, C., Ung, C. Y., Tripodis, Y., Kanaan, N. M., Ikezu, T., Cottone, P., Leszyk, J., Li, H., Luebke, J., Bryant, C. D., & Wolozin, B. Reducing the RNA binding protein T1A1 protects against tau-mediated neurodegeneration in vivo, Nature Neuroscience, January 1, 2018, Read More

Jiang, L., Ash, P. E. A., Maziuk, B. F., Ballance, H. I., Boudeau, S., Abdullatif, A. A., Orlando, M., Petrucelli, L., Ikezu, T., & Wolozin, B. TIA1 regulates the generation and response to toxic tau oligomers, Acta Neuropathologica, February 11, 2019, Read More

Ikezu, S., Ingraham Dixie, K. L., Koro, L., Watanabe, T., Kaibuchi, K., & Ikezu, T. Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models, Acta Neuropathologica Communications, February 4, 2020, Read More

Delpech, J. C., Herron, S., Botros, M. B., & Ikezu, T. Neuroimmune crosstalk through extracellular vesicles in health and disease, Trends in Neurosciences, March 26, 2019, Read More

Yeh, H., & Ikezu, T. Transcriptional and Epigenetic Regulation of Microglia in Health and Disease, Trends in Molecular Medicine, December 12, 2018, Read More

Delpech, J. C., Pathak, D., Varghese, M., Kalavai, S. V., Hays, E. C., Hof, P. R., Johnson, W. E., Ikezu, S., Medalla, M., Luebke, J. I., & Ikezu, T. Wolframin-1-expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice, Science Translational Medicine, September 15, 2021, Read More

You, Y., Botros, M. B., Enoo, A. A. V., Bockmiller, A., Herron, S., Delpech, J. C., & Ikezu, T. Cre-inducible Adeno Associated Virus-mediated Expression of P301L mutant tau causes motor deficits and neuronal degeneration in substantia nigra, Neuroscience, November 2, 2019, Read More

You, Y., & Ikezu, T. Emerging Role of Extracellular Vesicles in Neurodegenerative Disorders, Neurobiology of Disease, June 20, 2019, Read More

Ruan, Z., Delpech, J. C., Venkatesan Kalavai, S., Van Enoo, A. A., Hu, J., Ikezu, S., & Ikezu, T. P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice, Molecular Neurodegeneration, August 18, 2020, Read More

Muraoka, S., Jedrychowski, M. P., Iwahara, N., Abdullah, M., Onos, K. D., Keezer, K. J., Hu, J., Ikezu, S., Howell, G. R., Gygi, S. P., & Ikezu, T. Enrichment of Neurodegenerative Microglia Signature in Brain-Derived Extracellular Vesicles Isolated from Alzheimer’s Disease Mouse Models., Journal of Proteome Research, February 3, 2021, Read More

You, Y., Borgmann, K., Edara, V. V., Stacy, S., Ghorpade, A., & Ikezu, T. Activated Human Astrocyte-Derived Extracellular Vesicles Modulate Neuronal Uptake, Differentiation and Firing, Journal of Extracellular Vesicles, December 26, 2019, Read More

Muraoka, S., Jedrychowski, M. P., Tatebe, H., DeLeo, A. M., Ikezu, S., Tokuda, T., Gygi, S. P., Stern, R. A., & Ikezu, T. Proteomic Profiling of Extracellular Vesicles Isolated from Cerebrospinal Fluid of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy, Frontiers in Neuroscience, October 9, 2019, Read More

Muraoka, S., Jedrychowski, M. P., Yanamandra, K., Ikezu, S., Gygi, S. P., & Ikezu, T. Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer’s Disease Patients: A Pilot Study, Cells, August 25, 2020, Read More

Ruan, Z., Pathak, D., Venkatesan Kalavai, S., Yoshii-Kitahara, A., Muraoka, S., Bhatt, N., Takamatsu-Yukawa, K., Hu, J., Wang, Y., Hersh, S., Ericsson, M., Gorantla, S., Gendelman, H. E., Kayed, R., Ikezu, S., Luebke, J. I., & Ikezu, T. Alzheimer’s disease brain-derived extracellular vesicles spread tau pathology in interneurons, Brain, November 27, 2020, Read More

Muraoka, S., Lin, W., Takamatsu-Yukawa, K., Hu, J., Ikezu, S., DeTure, M. A., Dickson, D. W., Emili, A., & Ikezu, T. Enrichment of Phosphorylated Tau (Thr181) and Functionally Interacting Molecules in Chronic Traumatic Encephalopathy Brain-derived Extracellular Vesicles, Aging and Disease, September 1, 2021, Read More

Muraoka, S., DeLeo, A. M., Yang, Z., Tatebe, H., Yukawa-Takamatsu, K., Ikezu, S., Tokuda, T., Issadore, D., Stern, R. A., & Ikezu, T. Proteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy, Aging and Disease, September 1, 2021, Read More

You, Y., Zhang, Z., Sultana, N., Ericsson, M., Martens, Y. A., Sun, M., Kanekiyo, T., Ikezu, S., Shaffer, S. A., & Ikezu, T. ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids, Science Advances, September 15, 2023, Read More

Yin, Z., Herron, S., Silveira, S., Kleemann, K., ... Ikezu, S., Ikezu, T., Butovsky, O. Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease, Nature Neuroscience, June 8, 2023, Read More

Shi, H., Yin, Z., Koronyo, Y., Fuchs, D. T., Sheyn, J., Davis, M. R., Wilson, J. W., Margeta, M. A., Pitts, K. M., Herron, S., Ikezu, S., Ikezu, T., Graham, S. L., Gupta, V. K., Black, K. L., Mirzaei, M., Butovsky, O., & Koronyo-Hamaoui, M. Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer’s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia, Acta Neuropathologica Communications, September 8, 2022, Read More

Zhang, Z., Yu, K., You, Y., Jiang, P., Wu, Z., DeTure, M. A., Dickson, D. W., Ikezu, S., Peng, J., & Ikezu, T. Comprehensive characterization of human brain-derived extracellular vesicles using multiple isolation methods: Implications for diagnostic and therapeutic applications, Journal of Extracellular Vesicles, August 10, 2023, Read More

Ruan, Z., Takamatsu-Yukawa, K., Wang, Y., Ushman, M. L., Labadorf, A. T., Ericsson, M., Ikezu, S., & Ikezu, T. Functional genome-wide short hairpin RNA library screening identifies key molecules for extracellular vesicle secretion from microglia, Cell Reports, May 10, 2022, Read More

You, Y., Muraoka, S., Jedrychowski, M. P., Hu, J., McQuade, A. K., Young-Pearse, T., Aslebagh, R., Shaffer, S. A., Gygi, S. P., Blurton-Jones, M., Poon, W. W., & Ikezu, T. Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer’s disease brain, Journal of Extracellular Vesicles, January 13, 2022, Read More