Guojun Bu, Ph.D.

Lo Ka Chung Charitable Foundation Professor of Science, Division of Life Science, the Hong Kong University of Science and Technology

Dr. Guojun Bu is a world-renowned neuroscientist and former Chair, Department of Neuroscience at Mayo Clinic. His other career appointments include Professor in Cell Biology and Neuroscience at the Washington University School of Medicine in St. Louis and Chief Scientific Officer at SciNeuro Pharmaceuticals. Dr. Bu received his B.S. degree in biology from Beijing Normal University and his Ph.D. degree in biochemistry from Virginia Tech. He is a leader in the field of APOE and APOE receptors, which play critical roles in the pathogenesis of Alzheimer’s disease (AD). His primary interest is to understand why APOE4 is a strong risk factor for Alzheimer’s disease and how this pathway can be targeted for therapy. His interests also extend to addressing the protective mechanisms of APOE2 and APOE rare variants. Among the pathogenic pathways contributing to aging and Alzheimer’s disease, Dr. Bu’s work addresses the roles of brain lipid metabolism, neuronal signaling, neuroimmunity focusing on TREM2 and APOE, mechanisms of proteinopathy, and cerebrovascular integrity and function. He has published over 350 articles and was named as a “Highly Cited Researcher” according to Web of Science. Dr. Bu has received numerous honors and awards including the Zenith Fellows Award from the Alzheimer’s Association, the Established Investigator Award from the American Heart Association, a MERIT award from the NIH, the Investigator of the Year award from the Mayo Clinic, and the MetLife Foundation Award for Medical Research in Alzheimer’s disease. He is an elected Fellow of the American Association for the Advancement of Science (AAAS), Founding Editor and Editor-in-Chief of Molecular Neurodegeneration, an Associate Editor for Science Advances, and is on the editorial board for Neuron.

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

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

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

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

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

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

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

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

Shinohara, M., Koga, S., Konno, T., Nix, J., Shinohara, M., Aoki, N., Das, P., Parisi, J. E., Petersen, R. C., Rosenberry, T. L., Dickson, D. W., & Bu, G. Distinct spatiotemporal accumulation of N-truncated and full-length amyloid-beta(42) in Alzheimer’s disease., Brain, November 17, 2017, Read More

Shinohara, M., Kanekiyo, T., Tachibana, M., Kurti, A., Shinohara, M., Fu, Y., Zhao, J., Han, X., Sullivan, P. M., Rebeck, G. W., Fryer, J. D., Heckman, M. G., & Bu, G. APOE2 is associated with longevity independent of Alzheimer’s disease, eLife, October 19, 2020, Read More

Wojtas, A. M., Sens, J. P., Kang, S. S., Baker, K. E., Berry, T. J., Kurti, A., Daughrity, L., Jansen-West, K. R., Dickson, D. W., Petrucelli, L., Bu, G., Liu, C. C., & Fryer, J. D. Astrocyte-derived clusterin suppresses amyloid formation in vivo, Molecular Neurodegeneration, November 27, 2020, Read More

Liu, C. C., Wang, N., Chen, Y., Inoue, Y., … Fryer, J. D., … Bu, G. Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease, Nature Immunology, October 19, 2023, 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

Zhong L, Zhang ZL, Li X, Liao C, Mou P, Wang T, Wang Z, Wang Z, Wei M, Xu H, Bu G, Chen XF. TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway, Frontiers in Aging Neuroscience, June 21, 2017, Read More

Wang X, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, Zheng Q, Gao Y, Luo H, Zhang X, Bu G, Hong W, Xu H. SNX27 Deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis, Journal of Neuroscience, December 14, 2016, Read More

Zhuang, K., Huang, C., Leng, L., Zheng, H., Gao, Y., Chen, G., Ji, Z., Sun, H., Hu, Y., Wu, D., Shi, M., Li, H., Zhao, Y., Zhang, Y., Xue, M., Bu, G., Huang, T. Y., Xu, H., & Zhang, J. Neuron-specific menin deletion leads to synaptic dysfunction and cognitive impairment by modulating p35 experssion, Cell Reports, July 17, 2018, 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

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

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

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

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

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

Painter, M. M., Atagi, Y., Liu, C. C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. TREM2 in CNS homeostasis and neurodegenerative disease, Molecular Neurodegeneration, September 4, 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

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

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

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

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

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

Liu, C. C., Tsai, C. W., Deak, F., Rogers, J., Penuliar, M., Sung, Y. M., Maher, J. N., Fu, Y., Li, X., Xu, H., Estus, S., Hoe, H. S., Fryer, J. D., Kanekiyo, T., & Bu, G. Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer’s disease, Neuron, September 18, 2014, Read More

Kanekiyo, T., Xu, H., & Bu, G. ApoE and Aβ in Alzheimer’s disease: accidental encounters or partners?, Neuron, February 19, 2014, Read More

Gan, M., Jiang, P., McLean, P., Kanekiyo, T., & Bu, G. Low-density lipoprotein receptor-related protein 1 (LRP1) regulates the stability and function of GluA1 α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in neurons, PLoS One, December 12, 2014, Read More

Zhong, L., Chen, X. F., Wang, T., Wang, Z., Liao, C., Wang, Z., Huang, R., Wang, D., Li, X., Wu, L., Jia, L., Zheng, H., Painter, M., Atagi, Y., Liu, C. C., Zhang, Y. W., Fryer, J. D., Xu, H., & Bu, G. Soluble TREM2 induces inflammatory responses and enhnaces microglial survival, Journal of Experimental Medicine, March 6, 2017, Read More

Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., Xu, Y., Wang, K., Li, J., Huang, R., Can, D., Xu, H., Bu, G., & Chen, X. F. Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2), Molecular Neurodegeneration, March 27, 2018, 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

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

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

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

Raulin AC, Martens YA, Bu G. Lipoproteins in the Central Nervous System: From Biology to Pathobiology, Annual Review of Biochemistry, March 18, 2022, Read More

Zhao N, Liu CC, Qiao W, Bu G. Apolipoprotein E, Receptors, and Modulation of Alzhiemer’s disease, Biological Psychiatry, March 14, 2017, Read More

Greenwood AK, Montgomery KS, Kauer N, Woo KH, Leanza ZJ, Poehlman WL, Gockley J, Sieberts SK, Bradic L, Logsdon BA, Peters MA, Omberg L, Mangravite LM. The AD Knowledge Portal: A Repository for Multi-Omic Data on Alzheimer’s Disease and Aging, Current Protocols in Human Genetics, October 21, 2020, Read More

Atagi, Y., Liu, C. C., Painter, M. M., Chen, X. F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., & Bu, G. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2), Journal of Biological Chemistry, September 15, 2015, Read More

Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease, Molecular Neurodegeneration, November 4, 2020, Read More

Raulin, A. C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C. C. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies, Molecular Neurodegeneration, November 8, 2022, Read More

Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M., Asmann, Y. W., Zhang, B., Bu, G., & Liu, C. C. Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination, Molecular Neurodegeneration, November 23, 2022, Read More

Zhao, N., Liu, C. C., Van Ingelgom, A. J., Linares, C., Kurti, A., Knight, J. A., Heckman, M. G., Diehl, N. N., Shinohara, M., Martens, Y. A., Attrebi, O. N., Petrucelli, L., Fryer, J. D., Wszolek, Z. K., Graff-Radford, N. R., Caselli, R. J., Sanchez-Contreras, M. Y., Rademakers, R., Murray, M. E., Koga, S., … Bu, G. APOE ε2 is associated with increased tau pathology in primary tauopathy, Nature Communications, October 22, 2018, Read More

Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C. C., & Bu, G. Apolipoprotein E and Alzheimer’s disease: pathobiology and targeting strategies, Nature Reviews Neurology, July 31, 2019, Read More

Li, Y., Macyczko, J. R., Liu, C. C., & Bu, G. ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer’s disease, Neurobiology of Aging, March 22, 2022, Read More

Zhao, N., Liu, C. C., Van Ingelgom, A. J., Martens, Y. A., Linares, C., Knight, J. A., Painter, M. M., Sullivan, P. M., & Bu, G. Apolipoprotein E4 impairs neuronal insulin signaling by trapping insulin receptor in the endosomes, Neuron, September 27, 2017, Read More

Liu, C. C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C. W., & Bu, G. ApoE4 Accelerates Early Seeding of Amyloid Pathology, Neuron, December 6, 2017, Read More

Raulin, A. C., Liu, C. C., & Bu, G. An assay to evaluate the capacity of cholesterol acceptors using BODIPY-cholesterol in cells, STAR Protocols, March 17, 2023, Read More

Ross, O. A., & Bu, G. A Novel Link between Trafficking and Lewy body disorder, The Lancet Neurology, June 7, 2018, Read More

Shinohara M, Kanekiyo T, Yang L, Linthicum D, Shinohara M, Fu Y, Price L, Frisch-Daiello JL, Han X, Fryer JD, Bu G. APOE2 eases cognitve declne during aging: clinical and pre-clinival evaluations, Annals of Neurology, March 29, 2016, 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