Takahisa Kanekiyo, M.D., Ph.D.

Assistant Professor of Neuroscience, Mayo Clinic

Takahisa Kanekiyo, M.D., Ph.D., is an Assistant Professor of Neuroscience at Mayo Clinic Jacksonville. Dr. Kanekiyo earned his M.D. and Ph.D. from Osaka University Graduate School of Medicine in Japan, and completed his postdoctoral training at the Washington University School of Medicine in St. Louis and Mayo Clinic Jacksonville. He has been studying the pathogenic pathways of age-related neurodegenerative diseases and neurovascular diseases. His current interest is to understand the roles of apolipoprotein E (apoE) and apoE receptors in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). He is also exploring AD pathogenesis using iPS cells from patients with the disease risk genes including APOE4 and ABCA7. Dr. Kanekiyo has received several awards including the New Investigator Research Grant from the Alzheimer’s Association and Scientist Development Grant from the American Heart Association.

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.

Raulin, A. C., Doss, S. V., Heckman, M. G., Craver, E. C., Li, Z., Ikezu, T. C., Sekiya, H., Liu, C. C., Martens, Y. A., Rosenberg, C. L., Kuchenbecker, L. A., DeTure, M., Reichard, R. R., Nguyen, A. T., Constantopoulos, E., Larsen, R. A., Kounaves, E. K., Murray, M. E., Dickson, D. W., Petersen, R. C., Bu, G., Kanekiyo, T. Impact of APOE on amyloid and tau accumulation in argyrophilic grain disease and Alzheimer’s disease, Acta Neuropathologica Communications, February 9, 2024, 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

Li, Z., Heckman, M. G., Kanekiyo, T., Martens, Y. A., Day, G. S., Vassilaki, M., Liu, C. C., Bennett, D. A., Petersen, R. C., Zhao, N., & Bu, G. Clinicopathologic Factors Associated With Reversion to Normal Cognition in Patients With Mild Cognitive Impairment, Neurology, May 17, 2022, Read More

Liu, C. C., Zhao, J., Fu, Y., … Kanekiyo, T., Fryer, J. D., … Bu, G. Peripheral apoE4 enhances Alzheimer’s pathology and impairs cognition by compromising cerebrovascular function, Nature Neuroscience, August 1, 2022, Read More

Yamazaki, Y., Shinohara, M., Shinohara, M., Yamazaki, A., Murray, M. E., Liesinger, A. M., Heckman, M. G., Lesser, E. R., Parisi, J. E., Petersen, R. C., Dickson, D. W., Kanekiyo, T., & Bu, G. Selective loss of cortical endothelial tight junction proteins during Alzheimer’s disease progression, Brain, February 15, 2019, Read More

Oatman, S. R., Reddy, J. S., Quicksall, Z., … Kanekiyo, T., … Bu, G., … Ertekin-Taner, N. Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins, Molecular Neurodegeneration, January 7, 2023, Read More

Aikawa, T., Holm, M. L., & Kanekiyo, T. ABCA7 and Pathogenic Pathways of Alzheimer’s Disease, Brain Sciences, February 5, 2018, Read More

Le, L. T. M., Thompson, J. R., Dehghani-Ghahnaviyeh, S., Pant, S., Dang, P. X., French, J. B., Kanikeyo, T., Tajkhorshid, E., & Alam, A. Cryo‐EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms, The EMBO Journal, December 9, 2022, Read More

Kanekiyo, T., & Bu, G. The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer’s disease, Frontiers in Aging Neuroscience, May 20, 2014, Read More

Zhao, J., Ikezu, T. C., Lu, W., Macyczko, J. R., Li, Y., Lewis-Tuffin, L. J., Martens, Y. A., Ren, Y., Zhu, Y., Asmann, Y. W., Ertekin-Taner, N., Kanekiyo, T., & Bu, G. APOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids, Stem Cell Research & Therapy, August 21, 2023, Read More

Martens, Y. A., Xu, S., Tait, R., Li, G., Zhao, X. C., Lu, W., Liu, C. C., Kanekiyo, T., Bu, G., & Zhao, J. Generation and validation of APOE knockout human iPSC-derived cerebral organoids, STAR Protocols, June 5, 2021, Read More

Liu, C. C., Yamazaki, Y., Heckman, M. G., Martens, Y. A., Jia, L., Yamazaki, A., Diehl, N. N., Zhao, J., Zhao, N., DeTure, M., Davis, M. D., Felton, L. M., Qiao, W., Li, Y., Li, H., Fu, Y., Wang, N., Wren, M., Aikawa, T., Holm, M. L., Oue, H., Linares, C., Allen, M., Carrasquillo, M.M., Murray, M.E., Petersen, R.C., Ertekin-Taner, N., Dickson, D.W., Kanekiyo, T., Bu, G. Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease, Alzheimer's & Dementia, August 22, 2020, Read More

Yamazaki, Y., Liu, C. C., Yamazaki, A., Shue, F., Martens, Y. A., Chen, Y., Qiao, W., Kurti, A., Oue, H., Ren, Y., Li, Y., Aikawa, T., Cherukuri, Y., Fryer, J. D., Asmann, Y. W., Kim, B. Y. S., Kanekiyo, T., & Bu, G. Vascular ApoE4 Impairs Behavior by Modulating Gliovascular Function, Neuron, December 14, 2020, Read More

Rogers, J. T., Liu, C. C., Zhao, N., Wang, J., Putzke, T., Yang, L., Shinohara, M., Fryer, J. D., Kanekiyo, T., & Bu, G. Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice, Neurobiology of Aging, February 9, 2017, Read More

Liu, C. C., Zhao, N., Yamaguchi, Y., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., & Bu, G. Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid beta clearance and aggregation in Alzheimer’s disease, Science Translational Medicine, March 30, 2016, Read More

Liu, C. C., Hu, J., Zhao, N., Wang, J., Wang, N., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., & Bu, G. Astrocytic LRP1 Mediates Brain A beta Clearance and Impacts Amyloid Deposition, Journal of Neuroscience, April 12, 2017, Read More

Aikawa T, Ren Y, Yamazaki Y, Tachibana M, Johnson MR, Anderson CT, Martens YA, Holm ML, Asmann YW, Saito T, Saido TC, Fitzgerald ML, Bu G, Kanekiyo T. ABCA7 Haplodeficiency Distrubs Microglial immune Responses in the Mouse Brain, Proceedings of the National Academy of Sciences of the United States of America, November 5, 2019, Read More

Kawatani, K., Holm, M. L., Starling, S. C., Martens, Y. A., Zhao, J., Lu, W., Ren, Y., Li, Z., Jiang, P., Jiang, Y., Baker, S. K., Wang, N., Roy, B., Parsons, T. M., Perkerson, R. B., 3rd, Bao, H., Han, X., Bu, G., & Kanekiyo, T. ABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism, Molecular Psychiatry, December 22, 2023, Read More

Inoue, Y., Shue, F., Bu, G., & Kanekiyo, T. Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease, Molecular Neurodegeneration, July 11, 2023, Read More

Zhao, J., Lu, W., Ren, Y., Fu, Y., Martens, Y. A., Shue, F., Davis, M. D., Wang, X., … Kanekiyo, T., Bu, G. Apolipoprotein E regulates lipid metabolism and alpha-synuclein pathology in human iPSC-derived cerebral organoids, Acta Neuropathologica, August 28, 2021, Read More

Tai, L. M., Thomas, R., Marottoli, F. M., Koster, K. P., Kanekiyo, T., Morris, A. W., & Bu, G. (2016). The role of APOE in cerebrovascular dysfunction, Acta Neuropathologica, February 16, 2016, Read More

Reddy, J. S., Allen, M., Ho, C. C. G., Oatman, S. R., İş, Ö., Quicksall, Z. S., Wang, X., Jin, J., Patel, T. A., Carnwath, T. P., Nguyen, T. T., Malphrus, K. G., Lincoln, S. J., Carrasquillo, M. M., Crook, J. E., Kanekiyo, T., Murray, M. E., Bu, G., Dickson, D. W., & Ertekin-Taner, N. Genome-wide analysis identifies a novel LINC-PINT splice variant associated with vascular amyloid pathology in Alzheimer’s disease, Acta Neuropathologica Communications, May 21, 2021, Read More

Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., & Bu, G. ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components, Arteriosclerosis, Thrombosis, and Vascular Biology, October 31, 2019, Read More

Tachibana M, Yamazaki Y, Liu CC, Bu G, Kanekiyo T. Pericyte implantation in the brain enhances cerebral blood flow and reduces amyloid-beta pathology in amyloid model mice, Experimental Neurology, October 26, 2017, Read More

Aikawa, T., Ren, Y., Holm, M. L., Asmann, Y. W., Alam, A., Fitzgerald, M. L., Bu, G., & Kanekiyo, T. ABCA7 Regulates Brain Fatty Acid Metabolism During LPS-Induced Acute Inflammation, Frontiers in Neuroscience, April 7, 2021, Read More

Zhao J, Davis MD, Martens YA, Shinohara M, Graff-Radford NR, Younkin SG, Wszolek ZK, Kanekiyo T, Bu G. APOE epsilon 4/ epsilon 4 diminishes neurotrophic function of human iPSC-derived astrocytes, Human Molecular Genetics, April 21, 2017, Read More

Shinohara, M., Shinohara, M., Zhao, J., Fu, Y., Liu, C. C., Kanekiyo, T., & Bu, G. 5-HT3 Antagonist Ondansetron Increases apoE Secretion by Modulating the LXR-ABCA1 Pathway, International Journal of Molecular Sciences, March 25, 2019, Read More

Oue, H., Yamazaki, Y., Qiao, W., Yuanxin, C., Ren, Y., Kurti, A., … Bu, G., & Kanekiyo, T. LRP1 in vascular mural cells modulates cerebrovascular integrity and function in the presence of APOE4, JCI Insight, April 10, 2023, Read More

Casey, C. S., Atagi, Y., Yamazaki, Y., Shinohara, M., Tachibana, M., Fu, Y., Bu, G., & Kanekiyo, T. Apolipoprotein E inhibits cerebrovascular pericyte mobility through a RhoA protein-mediated pathway, Journal of Biological Chemistry, April 22, 2015, Read More

Shinohara, M., Tachibana, M., Kanekiyo, T., & Bu, G. Role of LRP1 in the pathogenesis of Alzheimer’s disease: evidence from clinical and preclinical studies, Journal of Lipid Research, April 4, 2017, Read More

Yang, L., Liu, C. C., Zheng, H., Kanekiyo, T., Atagi, Y., Jia, L., Wang, D., N'songo, A., Can, D., Xu, H., Chen, X. F., & Bu, G. LRP1 modulates the microglial immune response via regulation of JNK and NF-kappa B signaling pathways, Journal of Neuroinflammation, December 8, 2016, Read More

Liu, C. C., Hu, J., Tsai, C. W., Yue, M., Melrose, H. L., Kanekiyo, T., & Bu, G. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain, Journal of Neuroscience, April 8, 2015, Read More

Sakae, N., Liu, C. C., Shinohara, M., Frisch-Daiello, J., Ma, L., … Bu, G & Kanekiyo, T. ABCA7 Deficiency Accelerates Amyloid-β Generation and Alzheimer’s Neuronal Pathology, Journal of Neuroscience, March 30, 2016, Read More

Wren, M. C., Zhao, J., Liu, C. C., Murray, M. E., Atagi, Y., Davis, M. D., Fu, Y., Okano, H. J., Ogaki, K., Strongosky, A. J., Tacik, P., Rademakers, R., Ross, O. A., Dickson, D. W., Wszolek, Z. K., Kanekiyo, T., & Bu, G. Frontotemporal dementia-associated N279K tau mutant disrupts subcellular vesicle trafficking and induces cellular stress in iPSC-derived neural stem cells, Molecular Neurodegeneration, September 15, 2015, Read More

Martens, Y. A., Zhao, N., Liu, C. C., Kanekiyo, T., Yang, A. J., Goate, A. M., Holtzman, D. M., & Bu, G. ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias, Neuron, March 16, 2022, Read More