Lee's research focuses on the
pathology of
neurodegenerative diseases, especially
Alzheimer's disease,
Parkinson's disease,
frontotemporal lobar degeneration (FTLD), and
amyotrophic lateral sclerosis (ALS). Together with her late husband
John Q. Trojanowski, Lee's studies challenged conventional belief that Alzheimer's disease is caused by aggregation of
amyloid plaques, and pointed to the
tau protein as a major player. The pair first reported in 1988 that the tau protein is a central component of protein aggregates associated with Alzheimer's disease (known as paired helical filaments). They also determined that abnormal
phosphorylation of the tau protein is responsible for the formation of
neurofibrillary tangles, which are aggregates of the tau protein, and found that healthy
mice had tau aggregates inside neurons and exhibited Alzheimer's symptoms when injected with pathological tau protein. In a more recent study, they connected the two major types of protein aggregates,
amyloid plaques and tau protein aggregates, where the former facilitates tau aggregation in mice. For Parkinson's disease, Lee and Trojanowski reported that another protein,
alpha-synuclein, is a major component of
Lewy bodies, which are protein aggregates found in
neurons of Parkinson's patients. They also discovered a type of
chaperone protein can reduce the death of neurons caused by alpha-synuclein built-up, and that similar to the tau protein and Alzheimer's, healthy neurons may take up
extracellular alpha-synuclein and become defective in function. Apart from these two relatively well-known neurodegenerative diseases, Lee and Trojanowski also studied FTLD, ALS, and
multiple system atrophy. In 2004, they associated alpha-synuclein in the
brain with multiple system atrophy. Two years later, they showed for the first time the
TDP43 protein was abnormally modified by phosphorylation and
ubiquitylation in FTLD and ALS. == Personal life ==