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

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SUMMARY

Research in the Molecular Neurotherapeutics Laboratory led by Tsuneya Ikezu, M.D., Ph.D., 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 vesicles and molecules in the central nervous system influence the pathology and progression of select neurodegenerative disorders such as Alzheimer's disease and frontotemporal dementia.

Focus areas

• Gene therapy of Alzheimer's disease. Dr. Ikezu's laboratory demonstrated the therapeutic effect of the central nervous system delivery of adeno-associated virus expressing anti-inflammatory cytokines, dominant negative chemokines, and neurogenic factors for restoring hippocampal neurogenesis and memory function in mouse models of Alzheimer's disease.
• Proteomic and biological characterization of extracellular vesicles. The Molecular Neurotherapeutics Lab established purification protocols of extracellular vesicles from brain tissues, cerebrospinal fluid and plasma. It also identified disease-specific protein markers by protein mass-spectroscopy and machine learning approaches. It did this using biospecimens from Alzheimer's disease and chronic traumatic encephalopathy, animal models of Alzheimer's disease and human iPSC-derived neurons, astrocytes, microglia-like cells and oligodendrocytes. Researchers also have demonstrated the potent tau seeding activity of human Alzheimer's disease brain-derived extracellular vesicles on propagation of tau pathology after inoculation into aged mouse brains. This suggests the acceleration of tau pathology by extracellular vesicle secretion.
• Microglia and neuroinflammation. Dr. Ikezu and his colleagues also made substantial contributions to the classification of the activation phenotype of microglia, a cell type of significant interest. These microglial activation phenotypes were originally adapted from the M0, M1 and M2 classification of macrophages. However, more recent works on the characterization of the microglial gene expression phenotype in disease conditions show that microglia are largely in homeostatic or disease-associated states. The studies identified miR-155, APOE and TREM2 as key molecules for shaping the neurodegenerative microglia, which are also genetically associated with Alzheimer's disease.

Significance to patient care

Dr. Ikezu's research from the Molecular Neurotherapeutics Lab on how CSF1R inhibitors affect Alzheimer's disease helped start new drugs and clinical trials. In addition, Dr. Ikezu's work on cloning and studying the protein TTBK1 identified it as a new target for drug development in Alzheimer's and related brain diseases.

Professional highlights

• International Organizing Committee, International Society for Extracellular Vesicles 2026 Annual Meeting, 2025-present.
• Editorial board, Molecular Neurodegeneration, 2024-present.
• Editorial board, Journal of Extracellular Vesicles, 2023-present.
• Foreign Council Member, Japan Society for Dementia Research, 2023-present.
• Zenith Fellows Award, Alzheimer's Association, 2025.
• Florida Investigator of the Year, Mayo Clinic, 2023.
• Standing member, Clinical Neuroimmunology and Brain Tumor study section, National Institutes of Health, 2018-2022.
• Jack Spivack Distinguished Scientist in Neuroscience, Boston University School of Medicine, 2018.
• Inge Grundke-Iqbal Award for Alzheimer's Research, Alzheimer's Association International Conference, 2016.
• Distinguished Scientist Award, University of Nebraska Medical Center, 2010.
• UNeMed Research Innovation Award, 2009.
• Vada Kinman Oldfield Alzheimer's Research Award, 2000.