Age is considered one of the greatest risk factors for developing Parkinson’s Disease, but the biological reasons behind this connection remain unclear.
“We know that with Parkinson’s Disease, age is a key risk factor. Most often, the disease develops in older adults, people who are in their 60’s or 70’s,” explains Johan Jakobsson, Professor of Neuroscience at Lund University. “Aging has something to do with the disease process. But we actually know very little about how and why.”
The new ASAP-funded project brings together research teams from Cambridge University in the United Kingdom, Lund University in Sweden, EPFL Lausanne in Switzerland, and Memorial Sloan Kettering Cancer Center in New York. The group will join the ASAP Collaborative Research Network (CRN), an international, multidisciplinary, and multi-institutional network working to address high-priority research questions about Parkinson’s disease. The team’s goal is to map how age-related changes in the brain’s epigenetics, biological processes that regulate how our genes are used, might influence Parkinson’s Disease.
Mapping epigenetic changes in the aging brain, in health and disease
“It is known that epigenetics are involved with aging. You can, just by measuring epigenetic patterns, determine your age quite well,” Johan Jakobsson says. “So it’s thought that in Parkinson’s Disease this process might be sped up, meaning you have a higher biological age.”
To investigate these mechanisms, the team will examine brain tissue from several groups: younger individuals, older individuals, people with advanced Parkinson’s disease, and individuals with incidental Lewy body disease, a condition in which early signs of Parkinson’s pathology are found after death, even though the person showed no symptoms during life. Comparing these groups will help the researchers understand how normal brain aging differs from aging in Parkinson’s Disease.
“Our studies will draw on 200–300 post-mortem brain samples from the Cambridge Brain Bank, making it one of the most extensive epigenetic aging studies of the Parkinson’s brain to date,” Johan Jakobsson highlights.
The researchers will also examine multiple brain regions, including those affected early in Parkinson’s and those that remain relatively unaffected. They will also study different cell types, such as neurons and astrocytes, to see whether some show specific signs of accelerated aging.
“Our hypothesis is that some brain regions have aged more quickly than other brain regions within the same individual,” Johan Jakobsson explains. “Though this is very explorative, we will investigate this in a large cohort of patient tissue samples and, in parallel, mimic this in stem cell-derived neurons grown in the lab.”
An international team with a common goal
Each institution involved in the project will contribute specialized expertise. At Lund University, Johan’s team will lead single-cell transcriptomic analysis and examine DNA methylation using long-read sequencing. In Cambridge, Professor Roger Barker and Dr. Annelies Quaegebeur, Director of the Cambridge Brain Bank, will handle tissue selection and conduct proteomics studies. At EPFL Lausanne, Professor Fides Zenk will apply a new method to study epigenetic changes at the single-cell level. Meanwhile, Professor Lorenz Studer, founding Director of the Center for Stem Cell Biology at Memorial Sloan Kettering Cancer Center, will use stem cell-derived neurons to model aging in the dish.
“The team is very exciting. We just happened to cross paths at meetings in different places of the world, but we realized that we have a joint interest and very complementary experience. So the team is very good,” Johan Jakobsson says.
The team, known as Team Barker, will be led by Roger Barker. The Lund node will play a key scientific and administrative role, with nearly a quarter of Team Barker’s budget (2.2 million USD) awarded to Professor Johan Jakobsson and his team, the Laboratory of Molecular Neurogenetics.
“Being part of the ASAP community allows us to work together as a team in a highly complementary way while becoming part of an outstanding network of internationally leading research groups,” highlights Laura Castilla-Vallmanya, Scientific Project Manager for Team Barker. “ASAP provides a unique environment to accelerate scientific discovery in the Parkinson’s disease field, with a clear focus on active collaboration, resource development, and data sharing.”
Toward a new understanding of Parkinson’s Disease
While therapeutic applications remain a longer-term goal, Johan believes the project has the potential to reshape how researchers view the relationship between aging and neurodegeneration.
“If we understand which aging processes are accelerated in disease, we might be able to block those and delay the start of the disease,” he explains. “Even delaying it by 20 years would make all the difference.”
