Virginia M.-Y. Lee, Ph.D.

The John H. Ware III Professor in Alzheimer's Research, Dept of Pathology and Laboratory Medicine; Director, Center for Neurodegenerative Disease, University of Pennsylvania

Dr. Lee is a world renowned leader in research on tau, alpha-synuclein and the beta-amyloid precursor protein and their pathobiological roles in such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and frontotemporal dementias. In particular, Dr. Lee is attempting to determine the pathogenic roles of the abnormal proteins comprising senile plaques, Lewy bodies and neurofibrillary tangles, major pathological lesions found in the brains of patients with Alzheimer's disease and other neurodegenerative diseases.


Funded Research

Project Description Researchers Funding
Passive Tau Immunology

Neurofibrillary tangles (NFTs) are biomarkers for Alzheimer’s disease and are the products of a breakdown in part of the structure of cells (Tau), leading to neural cell death. The goal of this project is to establish the first cellular system that develops authentic NFT-like Tau aggregates to provide mechanistic insights into NFT pathogenesis and a potential tool for identifying Tau- based therapeutics.

2010 to 2011

Oligomer Collaborative Projects

A collaboration of members of the Research Consortium, a member of the Cure Alzheimer’s Fund Science Advisory Board and non-Cure Alzheimer’s Fund-affiliated researchers hypothesizes that an abnormal increase in levels of synaptic Abeta and, particularly, Abeta oligomers may lead to synaptic dysfunction, cognitive decline and eventually dementia. This highly innovative collaborative project will address how Abeta oligomers are formed and which types detrimentally impact synaptic dysfunction and neuronal survival in the brain.

2006 to 2008


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
Yuk Yee Leung, Jon B. Toledo, Alexey Nefedov, Robi Polikar, Nandini Raghavan, Sharon X. Xie, Michael Farnum, Tim Schultz, Young Baek, Vivianna M. Van Deerlin, William T. Hu, David M. Holtzman, Anne M. Fagan, Richard J. Perrin, Murray Grossman, Holly D. Soares, Mitchel A. Kling, Matthew Mailman, Steven E. Arnold, Vaibhav A. Narayan, Virginia M-Y. Lee, Leslie M. Shaw, David Baker, Gayle M. Wittenberg, John Q. Trojanowski, and Li-San Wang, Identifying amyloid pathology–related cerebrospinal fluid biomarkers for Alzheimer's disease in a multicohort study, Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 1(3), September 2015, 339-348
Michiyo Iba, Jing L. Guo, Jennifer D. McBride, Bin Zhang, John Q. Trojanowski, Virginia M.-Y. Lee, Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy, J NeuroScience, 33(3), January 16, 2013, 1024-1037
Jing L. Guo and Virginia M.-Y. Lee, Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles, The Journal of Biological Chemistry, 286/17, March 3, 2011, 15317-15331
Hu WT, McMillan C, Libon D, Leight S, Forman M, Lee VM-Y, Trojanowski JQ, Grossman M, Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia, Neurology, 75(7), Aug 17, 2010, 595-602
Choi SH, Leight SN, Lee VM-Y, Li T, Wong PC, Johson JA, Saraiva MJ, Sisodia SS, Accelerated Aβ Deposition in APPswe/PS1∆E9 Mice with Hemizygous Deletions of TTR (Transthyretin), J Neurosci, (26), 2007, 7006-7010