New research reveals the complex changes happening in different cell types in the brain that are affected by Parkinson's and identifies a unique population of neurons.

A hallmark of Parkinson's disease (PD) is the death of brain cells called dopaminergic neurons in a part of the brain called the substantia nigra. For people with Parkinson’s, these neurons stop producing dopamine, which helps control the body's movements and moods. However, it’s not clear if other types of cells are also affected.

A new study published in Science Advances identifies a new type of neuron associated with Parkinson’s. By looking at which genes were turned on and off in hundreds of thousands of different cells in the substantia nigra, the researchers developed an “atlas of gene expression.” This research may help us better understand Parkinson’s, and possibly help guide the development of new treatments.

This study was led by the Parkinson’s Foundation 2022 Research Centers Principal Investigator Zhenyu Yue, PhD, and co-Investigators Joel Blanchard, PhD, John Crary, MD, PhD and Bin Zhang, PhD, from Icahn School of Medicine at Mount Sinai.

About the Study & Results

The researchers studied gene expression in 315,867 cells from the substantia nigra of people who did or did not have Parkinson's. Within the samples, the researchers identified various known cell types, including different types of neurons and other brain cells.

Interestingly, the scientists found a unique group of neurons that had an activated gene called RIT2, which past studies had shown is associated with Parkinson's risk. These cells lacked markers of other common cell types in the substantia nigra, indicating that they may be a newly recognized cell population.

However, in people who had advanced Parkinson’s, RIT2 expression was decreased compared to those without Parkinson’s, suggesting that reduced RIT2 expression may play a role in the development of Parkinson's. This may also indicate that the unique population of RIT2 neurons may be more vulnerable to the disease.

The team assembled their data on gene expression to create an atlas of different populations of single cells in the substantia nigra, which can be used to explain changes associated with Parkinson’s. They found distinct patterns of changes in gene expression in the cells marked by RIT2. Moreover, the team identified pathways of cell-to-cell communication that were altered in Parkinson’s.

Research Takeaways

The researchers are hopeful that this new data will be useful in future research. For example, while many dopaminergic neurons were lost due to advanced Parkinson’s by the time these samples were collected, many survived — their atlas may eventually help reveal what makes some neurons more resilient.

They also hope that this data will help:

• Understand pathogenic mechanisms (how Parkinson’s works)
• Identify new therapeutic targets
• Help find clinical biomarkers for Parkinson’s. A PD biomarker would lead to faster and more accurate diagnosis and the ability to track PD progression. Right now, there is no single biomarker for Parkinson’s.

Highlights

• A unique group of neurons in the substantia nigra is marked by an activated gene, called RIT2, which past studies have shown is associated with Parkinson's risk. These cells did not have markers of other known cell types, indicating that they had not been previously identified.
• In people who had advanced Parkinson’s, RIT2 gene expression was reduced, which suggests it may play a role in the development of Parkinson's. It may also mean that the unique population of RIT2 neurons may be more vulnerable to the disease.
• Data was converted into an “atlas of gene expression” that identifies a broad range of gene expression patterns within the cells of the substantia nigra.

What does this mean?

This research is a step towards better understanding the changes that occur in the substantia nigra during Parkinson’s. Knowing that there is a new population of brain neurons tied to Parkinson’s — in addition to the well-established dopaminergic neurons ­— will provide researchers with new targets to develop different PD medications. These neurons can also lead to the development of a new biomarker, which could be a breakthrough in PD diagnosis and progression tracking.

What do these findings mean to the people with PD right now?

While this study does not impact people with PD right now, the PD community can find hope in that researchers are still discovering more about this disease, and how it works. We can only solve a puzzle if we have all the pieces, and this new piece contributes to the overall battle to beat Parkinson’s.

People who are concerned that they may be experiencing Parkinson’s symptoms should talk to a healthcare provider.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

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In 2023, Moving Day, A Walk for Parkinson’s, Parkinson’s Revolution and Parkinson’s Champions raised a record-breaking $8.8 million to advance research, improve access to care and provide life-changing resources to people with PD and their loved ones.

Meet four fundraisers and volunteers who inspire us:

Volunteering Helps Kathleen Find Community and Comfort

“I saw right away that Moving Day was more than just a walk, and I wanted to see how it changes people. I also wanted to help raise even one extra dollar for research so that the next person to get diagnosed doesn’t feel like I did. I want them to feel that there is hope.”

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Allie Takes Action Against PD Diagnosis through Parkinson’s Revolution

 “Part of my goal is pushing for a cure for Parkinson’s and making sure people are aware of it, but the other part is finding people who look like me. The Parkinson’s Revolution ride reminded me I have a long road ahead but right now, I’m fighting and feeling great.”

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Karan Completes Remarkable World Marathon Challenge for His Father

“One of the lessons my dad taught me early on is you’re meant to test your limits and if you’re going to do that, find a cause that’s near and dear to your heart and raise awareness and money for it.”

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Cornerstone Parkinson’s Fit Community Combats Parkinson’s By Moving Together

“We love Moving Day. We all think the Parkinson’s Foundation is important because they have so much to offer people with Parkinson’s. When someone new comes to the gym, the first thing I tell them is to connect with the Foundation and use their resources. We are so happy we can help raise money to support the Parkinson’s Foundation.”

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As researchers advance treatments for Parkinson’s disease (PD), there is a critical need to engage with the Parkinson’s community early and often during the research process. Populations of focus — including Black and African Americans, hispanics/latinos, women and others — are often underrepresented in, and historically excluded from, research. Engaging these communities in the development of drugs and the design of clinical trials creates an opportunity for greater representation in research. The Parkinson’s Foundation is committed to making research inclusive and creating a systemic change in the PD research space.

In September 2023, the Parkinson’s Foundation hosted a new, tailored version of its Learning Institute, which trains people with Parkinson’s and care partners in research and advocacy to work alongside scientists and government agencies in the drug development process.

Held in Atlanta, GA, in collaboration with Morehouse School of Medicine, the new training sought to engage the Black and African American Parkinson’s community (people with Parkinson’s, care partners, neurologists and professionals). During a three-day training, participants found community, learned how to confidently work alongside researchers and use their voice to advocate for changes in research.

“As a Foundation, we are actively creating programs and developing partnerships that will advance health equity for populations of focus,” said Evelyn Stevens, senior director of community engagement at the Parkinson’s Foundation. “We designed this educational and interactive training to deepen our understanding of the current needs of Black and African American people living with Parkinson's, and their care partners.”

The training included exclusive insight into the Foundation’s global genetics initiative, PD GENEration: Mapping the Future of Parkinson’s, and the opportunity to enroll and receive on-site genetic testing as part of the study. Before the training, 29% of attendees had reported participating in a research study. By the end of the Learning Institute, 100% of participants with Parkinson's had completed their first research study, PD GENEration. 

“Being part of the faculty for the Learning Institute to advance health equity in Parkinson’s care for the African American community was remarkable.”

- Reversa Joseph, MD, movement disorders specialist at Chalmers P. Wylie Veterans Outpatient Clinic

“I was honored to present on ethics in research as it was vital to empower participants with an understanding of the research process, enabling them to make informed decisions about clinical trial participation,” said Dr. Joseph. 

Ensuring diversity and inclusivity in Parkinson’s research is critical to accelerating breakthroughs toward a cure, which is why PD GENEration is designed to increase racial diversity among participants. In 2023, it announced Morehouse School of Medicine as the first historically Black institution of medicine to become a PD GENEration research site (read the article).

As of January 2024, 14.9% of PD GENEration participants are racially diverse. For perspective, U.S. clinical trials generally achieve less than 2% of diversity among participants.

“PD GENEration has established a strong relationship with the community through engagement and programs,” said Amasi Kumeh, director of research partnerships at the Parkinson’s Foundation. “We have become a gateway to research, helping recruit diverse participants for clinical trials and providing information about the process.”

The Learning Institute also emphasized community. The YMCA of Metro Atlanta, The Center for Movement Challenges, and a physical therapist from Emory University hosted a movement break for attendees, as exercise is proven to help people with PD manage symptoms. On the final afternoon, community members of Atlanta were invited to learn more about PD, get resources and meet the graduates of new class of 2023 Research Advocates.

No Topic Off-Limits

Black and African Americans experience health disparities when navigating Parkinson’s from day one — and are more likely to be diagnosed later in the disease stage than white people. Knowing this, the event was designed to welcome open conversation. “We wanted to provide a safe space for everyone to share their experiences and learn from one another,” Evelyn said.

For the first time, roundtable discussions were hosted. Every table was assigned a PD expert, neurologist or Parkinson’s Foundation staff member to lead a PD topic — from symptom management to best ways to reach the Black and African American community and how to connect people to PD resources.

“The moment that I stepped into the conference room for my first day of training, I knew this would be a life-changing experience.”

- Vanessa Russell Palmer, a person with Parkinson’s and Learning Institute attendee

“Interacting with other African Americans with Parkinson's, neurologists that look like me and sharing our daily challenges was empowering," said Vanessa. Becoming a Parkinson's Foundation Research Advocate has provided me with a new village of support, and I feel empowered to fight this disease every day and to work to bring more information about Parkinson's research and access to care to the African American community.”

Discussing the ethics of research was central to the training, directly addressing medical mistrust and the historical mistreatment the community has experienced in research and care. “Understanding past mistakes is crucial to preventing their recurrence, and it was rewarding to highlight the oversight that is now in place to ensure ethical research practices. Discussing the root causes of medical mistrust is necessary for acknowledgment and progress, fostering a path towards informed and empowered healthcare decisions,” said Dr. Joseph.

Through this training and other initiatives, the Foundation aims to continue addressing the ethical barriers associated with research in its effort to help all people live better with Parkinson’s.

Diversifying Research

Diversity in research accelerates the rate that researchers can better understand PD and drives better outcomes for the entire PD community. Research advocates return to their communities, activated and inspired to raise awareness and educate their community about the importance of taking part in clinical trials. “Diversifying research gets us one step closer in our efforts to advance treatments and find a cure for Parkinson’s disease.” said Evelyn.

Next, the Parkinson’s Foundation is working to tailor more trainings and local educational events to populations of focus. As with every Foundation event, the focus remains to ensure all people with PD and their families have what they need to manage this disease and live better with Parkinson’s.

Help spread Parkinson's awareness and register to attend a local event today. 

A new study indicates that tiny particles of polystyrene can promote the clumping of a protein involved in Parkinson’s.

Plastic waste is a growing problem, and as plastics break down the pieces can be problematic. A new study in Science Advances suggests that tiny plastic particles may be the latest environmental contributor to Parkinson’s disease (PD).

Microplastics are defined as particles smaller than 5 millimeters in diameter — for comparison, a grain of rice is 6 millimeters— and can also include nanoplastics (less than 1 micrometer). According to past research, it is common for blood samples to contain polystyrene nanoparticles, which come from pieces of foam packing materials, cups and cutlery. Research has also shown that unlike other kinds of plastic, polystyrene nanoparticles can enter the brain.

Parkinson’s disease is diagnosed when a protein, called alpha-synuclein, begins to clump in vulnerable neurons in the brain. The clumping ultimately affects dopamine, the neurotransmitter that gets progressively lost in PD, leading to early signs of the disease. This new study shows that polystyrene nanoparticles can interact with alpha-synuclein and promote its clumping in test tubes, in brain cells grown in a petri dish, and in mice.

About the Study & Results

Nanoplastic contaminants promote alpha-synuclein clumping.

Researchers mixed alpha-synuclein “seeds” with nanoplastics in test tubes to see if the presence of nanoplastics triggered the clumping of alpha-synuclein. After three days, they observed that, when combined with alpha-synuclein seeds, the nanoplastics promoted the acceleration of alpha-synuclein clumping formations.

Nanoplastic contaminants interact with alpha-synuclein at very specific regions of the protein.

Using computer modeling, the research team predicted a strong interaction between polystyrene nanoparticles and a region of alpha-synuclein. To validate this prediction, the team created a shortened version of alpha-synuclein that lacked the region the nanoparticles were predicted to interact with. Without that part of alpha-synuclein, the nanoparticles did not stick to the protein in lab experiments, indicating that the computer model was accurate.

Nanoplastic contaminants accelerate alpha synuclein clumping in neurons.

In mouse neurons grown in a petri dish, the researchers observed that nanoplastics were internalized into a specific compartment within the cell, called the lysosome, where alpha-synuclein tends to clump. They found that the nanoplastics accelerated the accumulation of pathogenic alpha-synuclein in these cells.

Nanoplastic contaminants accelerate alpha synuclein clumping in the mouse brain.

The researchers injected alpha-synuclein seeds and nanoplastics into the brains of live mice and found that about 20% of dopaminergic neurons — those thought to be crucial in the development of Parkinson’s — internalized both. Injecting the combination into mice led to an increase in alpha-synuclein clumps in dopaminergic neurons and an increase in alpha-synuclein pathology (as measured by molecular markers) compared to injecting the seeds alone. In 3 of 10 mice injected, nanoplastics alone led to alpha-synuclein pathology.

Traces of polystyrene can be found in human brain tissues. Finally, in brain tissue samples obtained from people with Lewy body dementia, a condition characterized by the presence of alpha-synuclein aggregates, the research team identified traces of polystyrene. This discovery suggests the potential presence of plastic nanoparticles in the human brain.

Highlights

•  Alpha-synuclein clumping was triggered and/or accelerated by nanoplastics in three different models — test tubes, brain cells grown in a petri dish and in mice brains.
• The interaction between polystyrene nanoparticles and alpha-synuclein occurs at a specific region in the alpha-synuclein protein.
• In brain tissue samples from people with Lewy body dementia, traces of polystyrene can be detected, suggesting that plastic nanoparticles may be present in human brains.

What does this mean?

Plastic waste may be contributing to Parkinson’s as an environmental factor. However, we do not yet know how such interactions might be happening in humans and whether the type of plastic might play a role.

What do these findings mean to the people with PD right now?

People are exposed to and consume microplastics every day, through breathing, eating foods and drinking liquids — whether they are packaged in plastic or not. Studies like this one are integral to disentangling how the effects of environmental toxicants contribute to the development of PD — we now know that polystyrene nanoparticles can make their way into the brain. Explore the environmental risk factors connected to Parkinson’s.

People who are concerned that they may be experiencing Parkinson’s symptoms should talk to a healthcare provider.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

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“I study the brain’s immune cells, called microglia,” said Lindsay Mitchell De Biase, PhD, from the University of California, Los Angeles. “Any population of neurons, including dopamine neurons, are intimately surrounded by and permeated by these cells. Whenever there is a challenge to the central nervous system, whether that is an injury or an infection, these cells change the way they function and interact with neurons.”

Through her 2021 Parkinson’s Foundation Stanley Fahn Junior Faculty Award, Dr. De Biase is studying how microglia influence vulnerability of dopamine neurons to Parkinson’s disease (PD). She and her research team hope to find ways to harness the transformative nature of microglia to preserve dopamine neurons and slow PD progression.

Microglial cells regulate central nervous system inflammation and the signaling connections between neurons. Emerging research suggests that mitochondria, organelles which generate the energy necessary to power cells, play an important role in regulating how microglia function. Understanding this interaction between mitochondria and microglial function, particularly the ability of these cells to influence the health of dopamine neurons, is where Dr. De Biase’s research comes into play.

“Many gene mutations that increase the risk for Parkinson’s are mutations in genes related to mitochondrial function,” said Dr. De Biase. “We think that some of these mutations are increasing disease risk, not only by affecting energy production within neurons, but by pushing microglial cells into a damaging, inflammatory state.”

Dr. De Biase is using novel technology to study the role of microglial mitochondria in a mouse model of PD. The intervention strategy she developed could be used in people who are at high risk for developing Parkinson’s, to delay disease development or prevent it. In people with PD, the strategy could create a more neuroprotective environment and preserve remaining dopamine neurons to delay PD progression.

Dr. De Biase’s research involves manipulating the function of microglia to see if it can protect midbrain dopamine neurons, which regulate movement, and play an important role in PD progression. Microglia play a key role in promoting neuronal health by mitigating overactivity and assisting in the formation of new connections between neurons. Dr. De Biase is working to harness these beneficial actions, seeking to “program” microglia to protect dopamine neurons and slow PD progression.

“Microglia are dynamic, malleable cells and could represent therapeutic targets that are highly distinct from others that have been explored thus far,” said Dr. De Biase.

“My greatest hope from our work comes from the fact that microglial cells are so dynamic,” she said. “These cells really can change their properties in many different contexts, and I think that makes them one of the most targetable cell populations in the brain. So, my hope is that what we are learning will reveal strategies that are really feasible for harnessing the neuroprotective abilities of these cells.”

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.