Cure Alzheimer's Fund Cure Alzheimer's Fund

Miranda Orr, Ph.D.

Associate Professor, Neurology, Washington University School of Medicine in St. Louis

Dr. Miranda Orr is an Associate Professor of Neurology at Washington University in St. Louis and a Research Health Scientist at the W.G. (Bill) Hefner VA Medical Center, Salisbury, NC. She is a translational neuroscientist with expertise that spans the biology of aging and tau-associated neurodegeneration. A primary goal of her research is to understand cellular and molecular processes driving neurodegeneration and cognitive impairment during the prodromal period associated with Alzheimer’s disease and related dementias. Her career has focused on tau neurobiology and its role as a cellular stress response at the intersection between healthy brain aging and neurodegeneration. Using this strategy, her laboratory has identified a link between tau pathology and cellular senescence, the quintessence of latent tissue degeneration. This seminal finding has laid the groundwork for further investigation into post-mitotic cellular senescence, a newly recognized neuronal cell fate; the interaction between fundamental cellular aging processes and neuronal pathology; and clinical trials using therapeutics to clear senescent cells.

To learn more, follow the Orr Lab on their social media page.

Related Research:

Investigating the Role of Tau Protein in Neuronal Senescence Miranda Orr 2024-01-12 Investigating the Role of Tau Protein in Neuronal Senescence Induction and Maintenance Miranda Orr 2020-11-04

Funded Research

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

Project Description Researchers Funding
Investigating the Role of Tau Protein in Neuronal Senescence 2024

$201,250
Investigating the Role of Tau Protein in Neuronal Senescence Induction and Maintenance 2021, 2022

$345,000

Selected Publications

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

Hudson, H. R., Sun, X., & Orr, M. E. Senescent brain cell types in Alzheimer’s disease: Pathological mechanisms and therapeutic opportunities, Neurotherapeutics, January 6, 2025, Read More

Richardson, T. E., Orr, M. E., Orr, T. C., Rohde, S. K., Ehrenberg, A. J., ... Goate, A. M., ... Kautz, T. F., … Walker, J. M. Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer’s disease, and primary age-related tauopathy hippocampi, Alzheimer's & Dementia, December 31, 2024, Read More

Riessland, M., Ximerakis, M., Jarjour, A. A., Zhang, B., & Orr, M. E. Therapeutic targeting of senescent cells in the CNS, Nature Reviews Drug Discovery, September 30, 2024, Read More

Orr M. E. A Need for Refined Senescence Biomarkers and Measures of Senolytics in the Brain, Journal of Alzheimer's Disease, March 19, 2024, Read More

Riessland, M., & Orr, M. E. Translating the Biology of Aging into New Therapeutics for Alzheimer’s Disease: Senolytics, Journal of Prevention of Alzheimer's Disease, October 24, 2023, Read More

Walker, J. M., Orr, M. E., Orr, T. C., ... Richardson, T. E. Spatial proteomics of hippocampal subfield-specific pathology in Alzheimer’s disease and primary age-related tauopathy, Alzheimer's & Dementia, September 30, 2023, Read More

Gonzales, M. M., Garbarino, V. R., Kautz, T. F., Palavicini, J. P., Lopez-Cruzan, M., Dehkordi, S. K., Mathews, J. J., Zare, H., Xu, P., Zhang, B., Franklin, C., Habes, M., Craft, S., Petersen, R. C., Tchkonia, T., Kirkland, J. L., Salardini, A., Seshadri, S., Musi, N., & Orr, M. E. Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial, Nature Medicine, September 7, 2023, Read More

Gonzales, M. M., Garbarino, V. R., Pollet, E., Palavicini, J. P., Kellogg, D. L., Jr, Kraig, E., & Orr, M. E. Biological aging processes underlying cognitive decline and neurodegenerative disease, Journal of Clinical Investigation, May 16, 2022, Read More

Walker, J. M., Kazempour Dehkordi, S., Fracassi, A., Vanschoiack, A., Pavenko, A., Taglialatela, G., Woltjer, R., Richardson, T. E., Zare, H., & Orr, M. E. Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling, Acta Neuropathologica Communications, February 14, 2022, Read More

Dehkordi, S. K., Walker, J., Sah, E., Bennett, E., Atrian, F., Frost, B., Woost, B., Bennett, R. E., Orr, T. C., Zhou, Y., Andhey, P. S., Colonna, M., Sudmant, P. H., Xu, P., Wang, M., Zhang, B., Zare, H., & Orr, M. E. Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology, Nature Aging, December 10, 2021, Read More

Sah, E., Krishnamurthy, S., Ahmidouch, M. Y., Gillispie, G. J., Milligan, C., & Orr, M. E. The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration, Life, March 11, 2021, Read More

Gillispie, G. J., Sah, E., Krishnamurthy, S., Ahmidouch, M. Y., Zhang, B., & Orr, M. E. Evidence of the Cellular Senescence Stress Response in Mitotically Active Brain Cells-Implications for Cancer and Neurodegeneration, Life, February 17, 2021, Read More

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