UPenn CNDR Receives $18M to Study Underlying Genetic Mechanisms of Alzheimer’s, Dementia & Parkinson’s Disease

UPenn CNDR Receives $18M to Study Underlying Genetic Mechanisms of Alzheimer’s, Dementia & Parkinson’s Disease

The Center for Neurodegenerative Disease Research (CNDR) at the University of Pennsylvania received $18.1 million to study the underlying genetic mechanisms that caused 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. Funded by the National Institute of Aging (NIA), the five-year grant will support four projects.

U.S. Demographics will Lead to Surge in Alzheimer’s, Dementia and Parkinson’s Disease

The U.S. becomes older by the year and by the 2030s all of the Baby Boomer generation will be 65 or older meaning 20% of America’s population will be of retirement age. By 2035 forecasts point to a 65+ population of 78 million.

With an aging population comes statistically more dementia whether Alzheimer’s Disease or others.  Presently, the Alzheimer’s Association believes there are 5.8 million Americans living with Alzheimer’s disease.  Already it is the sixth leading cause of death in the United States. Nearly 80% of Alzheimer’s patients also develop dementia. 

The Alpha-Synuclein Connection

Both of these diseases impact language and memory whereas Parkinson’s mainly affects motor skills. The three diseases are often associated with each other and previous CNDR research reveals 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. Affecting chemicals in the brain can lead to problems with thinking, movement, behavior, and mood.

The Penn Medicine team proposes that as alpha-synuclein proteins become misfolded and cluttered they become a prime suspect for these diseases. One pattern of misfolded proteins could lead to Alzheimer’s while another one to Dementia reports John Q. Trojanowski, MD, Ph.D., the William Maul Measey-Pathology and Laboratory Medicine at Penn Medicine; as well as co-director and co-founder of the CNDR.

Four Projects to Monitor

The grant will inject four projects with the capital needed for critically important scientific inquiries. The projects include:

·Evaluation of alpha-synuclein in test tubes and cell cultures to better understand how misfolding occurs and how specific shapes are created

·Mimic the first project in animal models to study the impact of these shapes on the progression of the disease. This effort will be directly led by Dr. Trojanowski.

The last two projects will move the work into the clinic.

·The third project will use imaging and antibodies to study how a patient who begins with Parkinson’s progresses to dementia and vice-versa. Dr. Murray Grossman, a professor of Neurology will lead and focus on the potential identification of biomarkers.

·The last project, led by Alice S. Chen-Plotkin, MD, focuses on tissue samples in an effort to identify genetic risk factors for these diseases. 

Lead Research/Investigators

This initiative includes a Core leadership team including:

John Q. Trojanowski, MD, Ph.D., the William Maul Measey-Pathology and Laboratory Medicine at Penn Medicine; as well as co-director and co-founder of the CNDR.

Daniel Weintraub, MD, professor of Psychiatry and fellow in Penn’s Institute of Aging

Sharon Xiangwen Xie, Ph.D., professor of Biostatistics and EpidemiologyCall to Action: Those with a professional interest in the potential underlying connections between Alzheimer’s Disease, Dementia, and Parkinson’s Disease should be aware of this study.