Cure Alzheimer's Fund Cure Alzheimer's Fund

Oleg Butovsky, Ph.D.

Howard L. Weiner Distinguished Chair in Neurology, Associate Professor, Harvard Medical School, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital

Dr. Butovsky’s major scientific interest is to understand the biology of resident microglia and peripheral inflammatory monocytes in homeostasis and neurodegenerative conditions. During his Ph.D. studies at the Weizmann Institute of Science, he investigated the role of microglia in regulating Aβ plaque deposition in AD models and the role of microglia in neurogenesis. He identified subpopulations of microglia and demonstrated how microglia can be both beneficial and detrimental in the context of neurodegeneration (PNAS, 2006; JCI 2006). Dr. Butovsky’s recent studies, published in JCI, 2012, Nat. Neurosci, 2014, J. Exp. Med. 2014, 2015, Nat. Neurosci, 2015 and Ann. Neurol. 2015, have identified a unique microglial signature in both mice and humans and are elucidating the relationship of microglia to CNS disease including AD, MS, and ALS. The above-mentioned findings prompted him to investigate further the role of innate immunity in AD. With the new knowledge gained, he hopes to address fundamental questions of the role of microglia in neurodegenerative conditions and apply this knowledge towards the development of novel immune-based targeting therapies for AD.

To learn more, visit the Butovsky Lab website and follow the research on social media @ButovskyLab and @OlegButovsky.

Information is also available on the websites of the Harvard Brain Science Initiative and the Harvard Immunology Program.

 

Related Research:

A New Model of Microglia Genetic Perturbation in Vivo to Screen All Risk Factors Associated with Alzheimer’s Disease Oleg Butovsky Vijay K. Kuchroo 2024-01-12 APOE Consortium: APOE4-Mediated Dysfunction of CD8 T-Cell-Microglia Crosstalk in Alzheimer’s Disease Oleg Butovsky 2022-11-16 The Role of MGnD-neurodegenerative Clec7a+ Microglia in an Alzheimer’s Disease Mouse Model Oleg Butovsky 2019-06-11 The Role of APOE in Microglia Regulation in Neurodegeneration Oleg Butovsky 2017-07-25

Funded Research

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

Project Description Researchers Funding
A New Model of Microglia Genetic Perturbation in Vivo to Screen All Risk Factors Associated with Alzheimer’s Disease 2023

$431,250
APOE Consortium: APOE4-Mediated Dysfunction of CD8 T-Cell-Microglia Crosstalk in Alzheimer’s Disease 2022, 2023

$575,000
The Role of MGnD-neurodegenerative Clec7a+ Microglia in an Alzheimer’s Disease Mouse Model 2019, 2021

$345,000
The Role of APOE in Microglia Regulation in Neurodegeneration 2017, 2018, 2020, 2021

$1,000,000

Selected Publications

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

Bosch, M. E., Dodiya, H. B., Michalkiewicz, J., Lee, C., Shaik, S. M., Weigle, I. Q., Zhang, C., Osborn, J., Nambiar, A., Patel, P., Parhizkar, S., Zhang, X., Laury, M. L., Mondal, P., Gomm, A., Schipma, M. J., Mallah, D., Butovsky, O., Chang, E. B., Tanzi, R. E., Gilbert, J. A., Holtzman, D. M. & Sisodia, S. S. Sodium oligomannate alters gut microbiota, reduces cerebral amyloidosis and reactive microglia in a sex-specific manner, Molecular Neurodegeneration, February 17, 2024, 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

Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., Krasemann, S., Lichtenthaler, S. F., Müller, S. A., Colombo, A., Monasor, L. S., Tahirovic, S., Herms, J., Willem, M., Pettkus, N., Butovsky, O., Bartenstein, P., Edbauer, D., Rominger, A., Erturk, A., Grathwohl, S. A., Neher, J. J., Holtzman, D., Meyer-Leuhmann, M., & Haass, C. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE, Nature Neuroscience, February 1, 2019, 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

Margeta, M. A., Yin, Z., Madore, C., Pitts, K. M., Letcher, S. M., Tang, J., Jiang, S., Gauthier, C. D., Silveira, S. R., Schroeder, C. M., Lad, E. M., Proia, A. D., Tanzi, R. E., Holtzman, D. M., Krasemann, S., Chen, D. F., & Butovsky, O. Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma, Immunity, August 16, 2022, Read More

Mazaheri, F., Snaidero, N., Kleinberger, G., Madore, C., Daria, A., Werner, G., Krasemann, S., Capell, A., Trümbach, D., Wurst, W., Brunner, B., Bultmann, S., Tahirovic, S., Kerschensteiner, M., Misgeld, T., Butovsky, O., & Haass, C. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury, EMBO Reports, May 8, 2017, Read More

Dodiya, H. B., Kuntz, T., Shaik, S. M., Baufeld, C., Leibowitz, J., Zhang, X., Gottel, N., Zhang, X., Butovsky, O., Gilbert, J. A., & Sisodia, S. S. Sex-specific effects of microbiome perturbations on cerebral amyloid beta amyloidosis and microglia phenotypes, Journal of Experimental Medicine, May 16, 2019, Read More

Wang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., Butovsky, O., Artyomov, M., Ulrich, J. D., & Holtzman, D. M. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia, Neuron, April 7, 2021, Read More

Krasemann, S., Madore, C., Cialic, R., Baufeld, C., ... Ulrich, J. D., … Lemere, C., Ikezu, T., ... Holtzman, D. M. … Haass, C., Butovsky, O. The TREM2-APOE Pathway drives the transcriptional phenotype of dysfunctional microglia in Neurodegenerative Diseases, Immunity, September 19, 2017, Read More

Butovsky, O., & Weiner, H. L. Microglia signatures and their role in health and disease, Nature Reviews Neuroscience, September 11, 2018, Read More

Baufeld, C., O'Loughlin, E., Calcagno, N., Madore, C., & Butovsky, O. Differential contribution of microglia and monocytes in neurodegenerative diseases, Journal of Neural Transmission, October 23, 2017, Read More

Roy, E. R., Wang, B., Wan, Y. W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., Lee, V. M., Trojanowski, J. Q., Ginsberg, S. D., Butovsky, O., Zheng, H., & Cao, W. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease, Journal of Clinical Investigation, March 9, 2020, Read More

Margeta, M. A., Letcher, S. M., Igo, R. P., Jr, Cooke Bailey, J. N., Pasquale, L. R., Haines, J. L., Butovsky, O., Wiggs, J. L., & NEIGHBORHOOD consortium Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4., Investigative Ophtalmology & Visual Science, July 1, 2020, Read More

Madore, C., Yin, Z., Leibowitz, J., & Butovsky, O. Microglia, Lifestyle Stress, and Neurodegeneration, Immunity, January 7, 2020, Read More

Fiore, N. T., Yin, Z., Guneykaya, D., Gauthier, C. D., Hayes, J. P., D'Hary, A., Butovsky, O., & Moalem-Taylor, G. Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury, Glia, January 20, 2022, Read More

Guneykaya, D., Ugursu, B., Logiacco, F., Popp, O., Feiks, M. A., Meyer, N., Wendt, S., Semtner, M., Cherif, F., Gauthier, C., Madore, C., Yin, Z., Çınar, Ö., Arslan, T., Gerevich, Z., Mertins, P., Butovsky, O., Kettenmann, H., & Wolf, S. A. Sex-specific microglia state in the Neuroligin-4 knock-out mouse model of autism spectrum disorder, Brain, Behavior, and Immunity, March 29, 2023, Read More

Kempthorne, L., Yoon, H., Madore, C., Smith, S., Wszolek, Z. K., Rademakers, R., Kim, J., Butovsky, O., & Dickson, D. W. Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy, Acta Neuropathologica Communications, May 19, 2020, Read More

Götzl, J. K., Brendel, M., Werner, G., Parhizkar, S., Sebastian Monasor, L., Kleinberger, G., Colombo, A. V., Deussing, M., Wagner, M., Winkelmann, J., Diehl-Schmid, J., Levin, J., Fellerer, K., Reifschneider, A., Bultmann, S., Bartenstein, P., Rominger, A., Tahirovic, S., Smith, S. T., Madore, C., Butovsky, O., Capell, A., & Haass, C. Opposite microglial activations stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism, EMBO Molecular Medicine, June 1, 2019, Read More

Paolicelli, R. C., Sierra, A., Stevens, B., et al. Microglia states and nomenclature: A field at its crossroads, Neuron, November 2, 2022, Read More

Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., Rojas, J. C., Gallardo, G., Wang, K., Roh, J., Robinson, G., Finn, M. B., Jiang, H., Sullivan, P. M., Baufeld, C., Wood, M. W., Sutphen, C., McCue, L., Xiong, C., Del-Aquila, J.L., Morris, J.C., Cruchage, C., Alzheimer's Disease Neuroimaging Initiative, Fagan, A.M., Miller, B.L., Boxer, A.L., Seeley, W.W., Butovsky, O., Barres, B.B., Paul, S.M., & Holtzman, D.M. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy, Nature, September 28, 2017, Read More

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