Sangram S. Sisodia, Ph.D.

Thomas Reynolds Sr. Family Professor of Neurosciences; Professor, Departments of Neurobiology and Neurology; Director, Center for Molecular Neurobiology, University of Chicago


Dr. Sisodia is a leading expert on the molecular and cell biology of Alzheimer’s disease pathology. He has been at the forefront of learning how the familial Alzheimer’s disease (FAD) genes, including the amyloid precursor protein and the presenilins, function normally, and contribute to Alzheimer’s disease pathogenesis. Most recently, Dr. Sisodia’s studies have shown that in mice, exercise has a remarkable ability to protect against Alzheimer’s disease pathology by favorably changing gene activity in the brain.

Related Research:

Microbiome Consortium: Temporal Relationships Between Gut Dysbiosis, Brain Amyloid Beta Metabolism and Microglia Cell Activation Following Antibiotic Treatment Sangram S. Sisodia 2023-11-02 Identifying the Sex-Specific Roles of the Gut Microbiome-Brain Axis in a Mouse Model of Amyloid Beta Amyloidosis Sangram S. Sisodia 2022-12-22 Temporal Relationships Between Gut Dysbiosis and Microglia Cell Activation Following Antibiotic Treatment Sangram S. Sisodia 2022-08-15 Effect of Gut Microbiome Dysbiosis on Neuroinflammation and Amyloid Beta Deposition: A Longitudinal Micro-PET Study in Alzheimer’s Transgenic Mice Sangram S. Sisodia 2020-12-15 Mechanisms By Which the Gut Microbiome Influences Amyloid Deposition and Neuroinflammation in the APPswe/ PS1DE9 Mouse Model of Amyloid Beta Amyloidosis Sangram S. Sisodia 2018-08-27 Mechanisms By Which the Gut Microbiome Influences Amyloid Deposition and Neuroinflammation in Mouse Models of Alzheimer’s Disease Sangram S. Sisodia 2016-07-05 In Vitro and In Vivo Analysis of APP Variants Sangram S. Sisodia 2016-04-26 The Role of Microbial Immune Responses in Alzheimer’s Disease Sangram S. Sisodia 2015-06-25 Investigations of the Mechanism of Action of TagretinR/Bexarotene on Amyloid Clearance in Transgenic Mouse Models Robert Vassar Sangram S. Sisodia 2012-12-12 Oligomer Collaborative Projects Charles Glabe David Holtzman Paul Greengard Rudy Tanzi Sam Gandy Sangram S. Sisodia Stephen Strittmatter Tae-Wan Kim Virginia Lee 2011-03-01 Molecular Mechanism Underlying Hippocampal Neurogenisis by Familial AD-linked Presenilin-1 Variants Sangram S. Sisodia 2011-02-11 Modulation of Abeta Deposition by Cell-Specific Mechanisms Sangram S. Sisodia 2011-02-11

Funded Research

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

Project Description Researchers Funding
Microbiome Consortium: Temporal Relationships Between Gut Dysbiosis, Brain Amyloid Beta Metabolism and Microglia Cell Activation Following Antibiotic Treatment 2023

$250,000

Identifying the Sex-Specific Roles of the Gut Microbiome-Brain Axis in a Mouse Model of Amyloid Beta Amyloidosis 2022, 2024

$427,158

Temporal Relationships Between Gut Dysbiosis and Microglia Cell Activation Following Antibiotic Treatment 2022

$229,033

Effect of Gut Microbiome Dysbiosis on Neuroinflammation and Amyloid Beta Deposition: A Longitudinal Micro-PET Study in Alzheimer’s Transgenic Mice 2020

$168,434

Mechanisms By Which the Gut Microbiome Influences Amyloid Deposition and Neuroinflammation in the APPswe/ PS1DE9 Mouse Model of Amyloid Beta Amyloidosis 2017

$175,000

Mechanisms By Which the Gut Microbiome Influences Amyloid Deposition and Neuroinflammation in Mouse Models of Alzheimer’s Disease 2016

$250,000

In Vitro and In Vivo Analysis of APP Variants 2016, 2017, 2019

$700,000

The Role of Microbial Immune Responses in Alzheimer’s Disease 2015

$250,000

Investigations of the Mechanism of Action of TagretinR/Bexarotene on Amyloid Clearance in Transgenic Mouse Models 2012

$50,343

Oligomer Collaborative Projects 2006

$1,550,000

Molecular Mechanism Underlying Hippocampal Neurogenisis by Familial AD-linked Presenilin-1 Variants 2008

$100,000

Modulation of Abeta Deposition by Cell-Specific Mechanisms 2010, 2011

$200,000

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

Zhang, X., Hoey, R. J., Lin, G., Koide, A., Leung, B., Ahn, K., Dolios, G., Paduch, M., Ikeuchi, T., Wang, R., Li, Y. M., Koide, S., & Sisodia, S. S. Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of gamma-secrtase using synthetic antibodies, Proceedings of the National Academy of Sciences of the United States of America, May 14, 2012, Read More

Zhang, X., Sullivan, E., Scimeca, M., Wu, X., Li, Y. M., & Sisodia, S. S. Evidence that the “Lid” domain of nicastrin is not essential for regulating secretase activity, Journal of Biological Chemistry, February 17, 2016, Read More

Wagner, S. L., Zhang, C., Cheng, S., Nguyen, P., Zhang, X., Rynearson, K. D., Wang, R., Li, Y., Sisodia, S. S., Mobley, W. C., & Tanzi, R. E. Soluble gamma-secretase modulators slectively inhibit the production of the 42 amino-acid amyloid beta peptide variant and augment the production of multiple carboxy-truncated amyloid beta species, Biochemistry, January 22, 2014, Read More

Zhang, X., Hoey, R., Koide, A., Dolios, G., Paduch, M., Nguyen, P., Wu, X., Li, Y., Wagner, S. L., Wang, R., Koide, S., & Sisodia, S. S. A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of gamma-secretase, Journal of Biological Chemistry, October 28, 2014, Read More

Choi, S. H., Li, Y., Parada, L. F., & Sisodia, S. S. Regulation of hippocampal progenitor cell survival, proliferation, and dendritic development by BDNF, Molecular Neurodegeneration, December 21, 2009, Read More

Meier, M., Kennedy-Darling, J., Choi, S. H., Norstrom, E. M., Sisodia, S. S., & Ismagilov, R. F. Plug-based microfluidics with defined surface chemistry to miniaturize and control aggregation of amyloidogenic peptides, Angewandte Chemie (International ed. in English), January 30, 2009, Read More

Ahn, K., Shelton, C. C., Tian, Y., Zhang, X., Gilchrist, M. L., Sisodia, S. S., & Li, Y. M. Activation and intrinsic gamma-secretase activity of presenilin 1, Proceedings of the National Academy of Sciences of the United States of America, November 29, 2010, Read More

Minter, M. R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M. W., Shen, X., Jabri, B., Chang, E. B., Tanzi, R. E., & Sisodia, S. S. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease, Scientific Reports, September 5, 2017, Read More

Veeraraghavalu, K., Zhang, C., Zhang, X., Tanzi, R. E., & Sisodia, S. S. Age-dependent, non-cell autonomous deposition of amyloid from synthesis of beta-amyloid by cells other than excitatory neurons, Journal of Neuroscience, March 5, 2014, Read More

Dodiya, H. B., Lutz, H. L., Weigle, I. Q., Patel, P., Michalkiewicz, J., Roman-Santiago, C. J., Zhang, C. M., Liang, Y., Srinath, A., Zhang, X., Xia, J., Olszewski, M., Zhang, X., Schipma, M. J., Chang, E. B., Tanzi, R. E., Gilbert, J. A., & Sisodia, S. S. Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia, Journal of Experimental Medicine, January 3, 2022, Read More

Dodiya, H. B., Frith, M., Sidebottom, A., Cao, Y., Koval, J., Chang, E., & Sisodia, S. S. Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer’s transgenic mice, Scientific Reports, May 18, 2020, Read More

Veetil, A. T., Zou, J., Henderson, K. W., Jani, M. S., Shaik, S. M., Sisodia, S. S., Hale, M. E., & Krishnan, Y. DNA-based fluorescent probes of NOS2 activity in live brains, Proceedings of the National Academy of Sciences of the United States of America, June 17, 2020, Read More

Veeraraghavalu, K., & Sisodia, S. S. Mutant presenilin 1 expression in excitatory neurons impairs enrichment-mediated phenotypes of adult hippocampal progenitor cells., Proceedings of the National Academy of Sciences of the United States of America, May 14, 2013, Read More

Choi, S. H., Veeraraghavalu, K., Lazarov, O., Marler, S., Ransohoff, R. M., Ramirez, J. M., & Sisodia, S. S. Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation, Neuron, August 28, 2008, Read More

Füger, P., Hefendehl, J. K., Veeraraghavalu, K., Wendeln, A. C., Schlosser, C., Obermüller, U., Wegenast-Braun, B. M., Neher, J. J., Martus, P., Kohsaka, S., Thunemann, M., Feil, R., Sisodia, S. S., Skodras, A., & Jucker, M. Microglia turnover with aging and in an Alzheimer’s model via long-term in vivo single cell imaging, Nature Neuroscience, August 28, 2017, Read More

Prinz, M., Priller, J., Sisodia, S. S., & Ransohoff, R. M. Heterogeneity of CNS Myeloid Cells and their roles in Neurodegeneration, Nature Neuroscience, September 27, 2011, Read More

Brunholz, S., Sisodia, S., Lorenzo, A., Deyts, C., Kins, S., & Morfini, G. Axonal Transport of APP and the spatial regulation of APP cleavage and function in neuronal cells, Experimental Brain Research, September 30, 2011, Read More

Main, B. S., & Minter, M. R. Microbial Immuno-Communication in Neurodegenerative Diseases, Frontiers in Neuroscience, March 23, 2017, Read More

Veeraraghavalu, K., Choi, S. H., Zhang, X., & Sisodia, S. S. Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone neuronal progenitors via cell-autonomous mechanisms involving Notch signaling, Journal of Neuroscience, May 19, 2010, Read More

Zhang, X., Garbett, K., Veeraraghavalu, K., Wilburn, B., Gilmore, R., Mirnics, K., & Sisodia, S. S. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2, Journal of Neuroscience, June 20, 2012, Read More

DeBoer, S. R., Dolios, G., Wang, R., & Sisodia, S. S. Differential release of ss-Amyloid from Dendrite versus Axon-targeted APP, Journal of Neuroscience, September 14, 2014, Read More

Veeraraghavalu, K., Choi, S. H., Zhang, X., & Sisodia, S. S. Endogenous expression of FAD-linked PS1 impairs proliferation, neuronal differentiation, and survival of adult hippocampal progenitors., Molecular Neurodegeneration, October 20, 2013, Read More

Shaik, S. M., Cao, Y., Gogola, J. V., Dodiya, H. B., Zhang, X., Boutej, H., Han, W., Kriz, J., & Sisodia, S. S. Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome, Molecular Neurodegeneration, December 16, 2023, Read More

Veetil, A. T., Chakraborty, K., Xiao, K., Minter, M. R., Sisodia, S. S., & Krishnan, Y. Cell-targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules, Nature Nanotechnology, August 21, 2017, Read More

Zhang, X., Zhang, C. M., Prokopenko, D., Liang, Y., Zhen, S. Y., Weigle, I. Q., Han, W., Aryal, M., Tanzi, R. E., & Sisodia, S. S. An APP ectodomain mutation outside of the Aβ domain promotes Aβ production in vitro and deposition in vivo, Journal of Experimental Medicine, June 7, 2021, Read More

Zhang, X., Zhang, C., Prokopenko, D., Liang, Y., Han, W., Tanzi, R. E., & Sisodia, S. S. Negative evidence for a role of APH1B T27I variant in Alzheimer’s disease, Human Molecular Genetics, April 15, 2020, Read More

Wei, W., Nguyen, L. N., Kessels, H. W., Hagiwara, H., Sisodia, S., & Malinow, R. Amyloid beta from axons and dendrites reduces local spine number and plasticity, Nature Neuroscience, 12/27/2009, 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

Cable, J., Holtzman, D. M., Hyman, B. T., Tansey, M. G., Colonna, M., Kellis, M., Brinton, R. D., Albert, M., Wellington, C. L., Sisodia, S. S., & Tanzi, R. E. Alternatives to Amyloid for Alzheimer’s Disease Therapies-A Symposium Report, Annals of the New York Academy of Sciences, May 29, 2020, Read More

Minter, M. R., Zhang, C., Leone, V., Ringus, D. L., Zhang, X., Oyler-Castrillo, P., Musch, M. W., Liao, F., Ward, J. F., Holtzman, D. M., Chang, E. B., Tanzi, R. E., & Sisodia, S. S. Antibiotic-induced perturbation in gut microbial diversity influences neuro-inflammation and amylodiosis in a murine model of Alzheimer’s disease, Scientific Reports, July 16, 2016, Read More

Saha, P., Weigle, I. Q., Slimmon, N., Poli, P. B., Patel, P., Zhang, X., Cao, Y., Michalkiewicz, J., Gomm, A., Zhang, C., Tanzi, R. E., Dylla, N., Al-Hendy, A., & Sisodia, S. S. Early modulation of the gut microbiome by female sex hormones alters amyloid pathology and microglial function, Scientific Reports, January 21, 2024, Read More

Whitson, H. E., Colton, C., El Khoury, J., Gate, D., Goate, A., Heneka, M. T., Kaddurah-Daouk, R., Klein, R. S., Shinohara, M. L., Sisodia, S., Spudich, S. S., Stevens, B., Tanzi, R., Ting, J. P., Garden, G., & Symposium Planning Committee members Infection and inflammation: New perspectives on Alzheimer’s disease, Brain, Behavior, & Immunity - Health, April 22, 2022, Read More