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Karen E. Duff, Ph.D.

UK DRI (Dementia Research Institute), Centre Director, University College London, England

With over 20 years’ experience working in Alzheimer’s disease, Dr. Karen Duff returned to the UK in 2020 as Centre Director of the UK DRI (Dementia Research Institute) hub in University College London.

After completing a Ph.D. in the University of Cambridge lab of Nobel Prize winner Sydney Brenner in 1991, Dr. Duff has become a leader in the field of neurodegenerative disease. She is best known for her work in the development of several transgenic research models, which have driven the field forward in its mission to find therapeutics for these devastating conditions.  Dr. Duff has genetically engineered several widely used mouse models for AD, tauopathies and synucleinopathies. These mice have been used in studies ranging from MRI and PET for diagnostics development, to proof-of-concept testing of therapeutic targets. Her main interests are fourfold – studying how AD-related pathology and dysfunction propagates through the brain and from cell to cell as the disease worsens; using multi-omics platforms (transcriptomics, lipidomics and metabolomics) to study the role of aging and inheritance of the AD risk variant APOE4 as an initiating factor in AD; the role and therapeutic potential of protein clearance pathways in tauopathies and the basis and manipulation of memory deficits using optogenetic and brain stimulation techniques.

After receiving her Ph.D. at the University of Cambridge (UK), she moved to London to work briefly with Alison Goate before moving to the US with John Hardy in 1992 to a position at the University of South Florida. In 1996, she moved her lab to the Mayo Clinic Florida and in 1998 to the Nathan Kline Institute/New York University before joining Columbia University in 2006. She has published over 140 peer-reviewed papers and has received several awards in addition to the prestigious Potamkin Prize in 2006.

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

Related Research:

Alzheimer’s Disease Tau Consortium: Post-Translational Modifications and Tau Ultrastructure; Impact of Amyloid Beta on Tau In Vivo Karen Duff René Frank 2024-12-23 Cellular Vulnerability to Pathological Tau Protein
Accumulation in Alzheimer’s Disease Mathieu Bourdenx Karen Duff 2024-03-18 Alzheimer’s Disease Tau Consortium: Impact of Tau Mutations and Amyloid Beta on Tau Post-Translational Modifications and Conformation Karen Duff 2023-01-18 Cellular Vulnerability to Aging in Alzheimer’s Disease Mathieu Bourdenx Karen Duff 2022-07-19 Investigating the Mechanism of APOE4-associated Neuronal Hyperactivity in the Entorhinal Cortex and its Effect on Tauopathy Propagation Karen Duff Tal Nuriel 2018-08-27 Propagation of Tauopathy and Ubiquitin Proteasome System Dysfunction: Impact and Rescue with a UPS Activator Karen Duff Natura Myeku 2017-03-01 Investigating the Mechanism of Entorhinal Cortex Hypermetabolism in APOE4 Targeted Replacement Mice Karen Duff Tal Nuriel 2016-05-12

Funded Research

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

Project Description Researchers Funding
Alzheimer’s Disease Tau Consortium: Post-Translational Modifications and Tau Ultrastructure; Impact of Amyloid Beta on Tau In Vivo 2024

$366,770
Cellular Vulnerability to Pathological Tau Protein
Accumulation in Alzheimer’s Disease		 2024, 2025

$449,650
Alzheimer’s Disease Tau Consortium: Impact of Tau Mutations and Amyloid Beta on Tau Post-Translational Modifications and Conformation 2022, 2023

$689,993.33
Cellular Vulnerability to Aging in Alzheimer’s Disease 2022

$230,000
Investigating the Mechanism of APOE4-associated Neuronal Hyperactivity in the Entorhinal Cortex and its Effect on Tauopathy Propagation 2017

$200,000
Propagation of Tauopathy and Ubiquitin Proteasome System Dysfunction: Impact and Rescue with a UPS Activator 2017

$320,106
Investigating the Mechanism of Entorhinal Cortex Hypermetabolism in APOE4 Targeted Replacement Mice 2016

$150,000

Selected Publications

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

Watamura, N., Foiani, M. S., Bez, S., Bourdenx, M., Santambrogio, A., Frodsham, C., Camporesi, E., Brinkmalm, G., Zetterberg, H., , … Duff, K. E., Saido, T. C. In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds, Nature Neuroscience, December 24, 2024, Read More

Schaler, A. W., Runyan, A. M., Clelland, C. L., Sydney, E. J., Fowler, S. L., Figueroa, H. Y., Shioda, S., Santa-Maria, I., Duff, K. E., & Myeku, N. PAC1 receptor-mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain, Science Translational Medicine, May 26, 2021, Read More

Nuriel, T., Peng, K. Y., Ashok, A., Dillman, A. A., Figueroa, H. Y., Apuzzo, J., Ambat, J., Levy, E., Cookson, M. R., Mathews, P. M., & Duff, K. E. The Endosomal-Lysosomal Pathway is Dysregulated by APOE4 Expression in Vivo, Frontiers in Neuroscience, December 12, 2017, Read More

Nuriel, T., Angulo, S. L., Khan, U., Ashok, A., Chen, Q., Figueroa, H. Y., Emrani, S., Liu, L., Herman, M., Barrett, G., Savage, V., Buitrago, L., Cepeda-Prado, E., Fung, C., Goldberg, E., Gross, S. S., Hussaini, S. A., Moreno, H., Small, S. A., & Duff, K. E. Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology, Nature Communications, November 13, 2017, Read More

Fu, H., Possenti, A., Freer, R., Nakano, Y., Hernandez Villegas, N. C., Tang, M., Cauhy, P. V. M., Lassus, B. A., Chen, S., Fowler, S. L., Figueroa, H. Y., Huey, E. D., Johnson, G. V. W., Vendruscolo, M., & Duff, K. E. A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology, Nature Neuroscience, December 17, 2018, Read More

Myeku, N., & Duff, K. E. Targeting the 26S Proteasome to Protect against Proteotoxic Diseases, Trends in Molecular Medicine, December 9, 2017, Read More

Fu, H., Hardy, J., & Duff, K. E. Selective vulnerability in neurodegenerative diseases, Nature Neuroscience, September 24, 2018, Read More

Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A., Herman, M., Nahmani, E., Emrani, S., Figueroa, Y. H., Diamond, M. I., Clelland, C. L., Wray, S., & Duff, K. E. Neuronal activity enhances tau propagation and tau pathology in vivo, Nature Neuroscience, June 20, 2016, Read More

Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R. R., Guilfoyle, D. N., Pirhaji, L., Shannon, K., Arain, H. A., Ashok, A., Chen, Q., Dillman, A. A., Figueroa, H. Y., Cookson, M. R., Gross, S. S., Fraenkel, E., Duff, K. E., & Nuriel, T. APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice, Scientific Reports, March 9, 2020, Read More

Miranda, A. M., Ashok, A., Chan, R. B., Zhou, B., Xu, Y., McIntire, L. B., Area-Gomez, E., Di Paolo, G., Duff, K. E., Oliveira, T. G., & Nuriel, T. Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice, Translational Psychiatry, March 29, 2022, Read More

Blaudin de Thé, F. X., Lassus, B., Schaler, A. W., Fowler, S. L., Goulbourne, C. N., Jeggo, R., Mannoury la Cour, C., Millan, M. J., & Duff, K. E. P62 accumulates through neuroanatomical circuits in response to tauopathy propagation, Acta Neuropathologica Communications, November 2, 2021, Read More

Taddei, R. N., Perbet, R., Mate de Gerando, A., Wiedmer, A. E., Sanchez-Mico, M., Connors Stewart, T., Gaona, A., Melloni, A., Amaral, A. C., Duff, K., Frosch, M. P., & Gómez-Isla, T. Tau Oligomer-Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease, JAMA Neurology, October 9, 2023, Read More

Capano, L. S., Sato, C., Ficulle, E., Yu, A., Horie, K., Kwon, J. S., Burbach, K. F., Barthélemy, N. R., Fox, S. G., Karch, C. M., Bateman, R. J., Houlden, H., Morimoto, R. I., Holtzman, D. M., Duff, K. E., & Yoo, A. S. Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons, Cell Stem Cell, June 2, 2022, Read More

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