On Sept. 30, 2019, UPenn’s Center for Neurodegenerative Disease Research (CNDR) announced it had received a grant expected to total $18.1 million to study the underlying genetic mechanisms that cause Alzheimer’s Disease, Dementia, and Parkinson’s Disease to progress as well as how those mechanisms are related to each other and to the cell-to-cell spread of these disease proteins. The grant, awarded by the National Institutes of Health’s National Institute on Aging (NIA), will fund four specific projects over the next five years.

The Alzheimer’s Association estimates there are 5.8 million Americans currently living with Alzheimer’s. It is the sixth leading cause of death in the United States. About 80 percent of Alzheimer’s patients also develop dementia. Both of these diseases affect language and memory, whereas Parkinson’s mainly affects motor skills. The three conditions are often associated with each other, and previous research from the CNDR and others has shown they share several underlying connections, including a connection to a protein called alpha-synuclein as well as Alzheimer’s Disease plaques and tangles. When normal alpha-synuclein proteins become misfolded and are not cleared away, they become deposits in the brain in the form of lesions known as Lewy bodies. They affect chemicals in the brain, which, in turn, can lead to problems with thinking, movement, behavior, and mood.

The grant will seek to further the team’s theory through four specific projects. The first project, led by Lee, will evaluate alpha-synuclein in test tubes and cell cultures in an effort to better understand how misfolding happens and how specific shapes are created. The second, led by Trojanowski, will mimic the first project in animal models to study the impact of these shapes on the progression of disease.