2025 Trailblazer Award 

Combining AI and Skin Biopsies to Detect Parkinson’s Years Earlier 

Parkinson’s disease (PD) is primarily diagnosed clinically, meaning that a diagnosis is based on an assessment of symptoms and medical history. While certain tests looking at PD biomarkers can help support a diagnosis, currently there is no specific lab test that can be used to diagnose PD by itself. Additionally, there is currently no way to efficiently predict who may be at risk for developing PD, which is critical for potential therapeutic interventions.  

Jay Alberts, PhD, recipient of a Parkinson’s Foundation Trailblazer Award, is leveraging an explainable artificial intelligence (AI) model to identify those at-risk for developing PD within two years based on medical history analysis. He will then invite those deemed “high-risk” to test out a new diagnostic test that could detect PD with a simple skin biopsy, improving our ability to detect the disease earlier. 

“This project leverages the power of artificial intelligence to provide greater understanding and use of a promising biomarker test in individuals who may be in the pre-symptomatic phase of PD.” – Dr. Alberts 

Alpha-synuclein, a protein whose biochemically altered form is prone to neuron-damaging clumping in PD, is widely agreed to be a strong candidate biomarker for the disease. Recent research has found that biochemically altered alpha-synuclein can readily be detected in skin samples of those with symptomatic PD. Dr. Alberts is working to see if the same is true of those with pre-symptomatic PD and if AI can best identify people who should undergo this testing. 

Dr. Alberts and his team at the Cleveland Clinic, a Parkinson’s Foundation Center of Excellence, have developed an AI program that can analyze health records to determine a person’s risk of developing PD within a few years. Importantly, the AI system is “explainable,” meaning that the model can inform patients on the relative contribution of each predicting factor that leads into their overall risk score.  

For his study, Dr. Alberts will invite people the AI model has deemed to be high and low risk of future PD to undergo a Syn-One test. This diagnostic test involves three small skin biopsies — each approximately 1/8 of a pencil eraser in size — from which levels of biochemically altered alpha-synuclein are measured. If Dr. Alberts’ hypothesis is correct, then those deemed high-risk for future PD will have higher amounts of this biomarker than those deemed low-risk.  

“This project will, for the first time, combine explainable artificial intelligence models developed from the electronic health record to identify and evaluate a scalable approach to screening for Parkinson's disease,” said Dr. Alberts.  

If these validation studies go well, this combination of AI-powered risk determination with Syn-One testing could be used to detect PD years earlier than currently possible. 

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

2025 Impact Award 

Investigating How Neurons Rebalance Their Roles in Early Parkinson’s 

In Parkinson’s disease (PD), cognitive symptoms often appear years before movement symptoms begin. However, these cognitive symptoms — difficulties performing tasks involving decision-making and learning — are linked to many different diseases and therefore difficult to use as an indicator for PD without additional clinical evidence. 

Kauê M. Costa, PhD, recipient of a Parkinson’s Foundation Impact Award, is diving into the complex neuroscience of PD to better understand what causes cognitive PD symptoms to occur before movement symptoms. This research could help lead to improved treatments for PD cognitive symptoms and support earlier PD diagnoses. 

“This research has the potential to shed light on intrinsic mechanisms of adaptation to cell loss that could be leveraged for developing new treatments for the disease, and to identify early biomarkers of Parkinsonian degeneration, which could be used for early diagnosis and intervention.” – Dr. Costa 

As PD progresses, dopamine-producing neurons in the substantia nigra region of the brain lose function and break down. The most fragile of these neurons, and usually the first ones to degenerate, are located in the lateral substantia nigra (lSN) and are important for sending movement signals to another brain region called the dorsolateral striatum (DSL). 

Dr. Costa hypothesizes that as these lSN neurons break down in early PD, the neighboring neurons in the medial substantia nigra (mSN) attempt to “pick up the slack”, taking over the lost movement signaling responsibilities. However, doing so means sacrificing efficiency in their other role, which involves cognitive signaling. This could explain why cognitive symptoms appear first, as the brain reorganizes neurons to preserve movement signaling at the expense of cognitive signaling. 

From his lab at the University of Alabama at Birmingham, Dr. Costa will test his hypothesis by measuring the abilities of rats to perform learning-based and movement tasks before and after they are induced with simulated PD. Using state-of-the-art brain monitoring technology, Dr. Costa will also record dopamine released by both lSN and mSN neurons over time, observing how they change and adapt as the simulated disease progresses and if they follow his prediction of reorganized signaling roles. 

By understanding what is happening in the brain in early PD to cause cognitive symptoms before movement ones, doctors could improve the ability to diagnose the disease earlier, treat cognitive symptoms more efficiently, and potentially delay additional symptoms.  

“This Impact Award will allow me to apply my expertise to solving an important question in Parkinson's disease pathology, which I have been thinking about since I was a graduate student,” said Dr. Costa. “I am grateful to the Parkinson's Foundation for the opportunity to pursue my interests in the intersection of basic and translational neuroscience.”  

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

2025 Impact Award 

Investigating New Ways to Address Posture Impairment in Parkinson’s 

A common symptom of Parkinson’s disease (PD) is impaired posture. Unfortunately, this symptom is resistant to standard dopamine replacement therapies, and not much is known about the neurological mechanisms that lead to it. Left unchecked, posture impairment can lead to serious falls and other injuries for people with PD. 

Colum MacKinnon, PhD, recipient of a Parkinson’s Foundation Impact Award, suspects that PD affects brainstem neurons responsible for sending posture-related signals to the muscles of the legs and feet. Investigating this potential mechanism behind PD-related posture impairment may contribute to future treatments that could alleviate this debilitating symptom. 

“If successful, this work will be the first to demonstrate that brainstem pathways that control muscle firing properties are altered in people with PD and are associated with postural impairment.” – Dr. MacKinnon 

Dr. MacKinnon, with the help of his coinvestigators Dr. Laura McPherson, PT, DPT, PhD, and Dr. Daniel Free, PhD, will enroll people with and without PD, recording and analyzing their posture and gait (walking manner). He will also use a device to measure muscle activity activity as they point and flex their feet, capturing nerve signals important for balance and posture. 

From this initial data collection, Dr. MacKinnon expects to see reduced postural muscle activity that is controlled by descending brainstem systems in people with PD, and this reduction will correlate with impaired posture and walking ability. 

Next, Dr. MacKinnon will use a noninvasive vagus nerve stimulation device, commonly used to treat migraines and cluster headaches, to stimulate neurons within the brainstem associated with postural control. If his hypothesis is correct, this stimulation will temporarily improve the posture and balance of those with PD as the signals to the ankle muscles are restored. These studies will provide valuable direction for future research and therapeutic development of PD-associated posture impairment, which could significantly improve quality of life for people with PD. 

 “This award provides the unique opportunity to explore the potential contributions of non-dopaminergic pathways to the abnormal muscle activation patterns observed in people with PD, and to conduct exploratory experiments to test the efficacy of using vagus nerve stimulation to upregulate these pathways, improve muscle activation, gait and postural control,” said Dr. MacKinnon. 

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

2025 Impact Award 

Untangling the Importance of Protein Clumping in Parkinson’s Cognitive Symptoms 

Parkinson’s disease (PD) is primarily known for its movement symptoms such as tremors, rigidity and slowness. However, most people with PD also develop other non-movement symptoms, including changes in thinking and memory.

Nuria Vendrell-Llopis, PhD, recipient of a Parkinson’s Foundation Impact Award, is uncovering whether the likely biological cause for PD movement symptoms also contributes to PD-linked thinking impairment. Understanding how movement and non-movement symptoms overlap or diverge could lead to new diagnostic and treatment tools for PD cognitive symptoms.

“Our research aims to investigate how the accumulation of alpha-synuclein, a protein associated with Parkinson’s disease, disrupts the brain circuits that support learning and other cognitive functions.” — Dr. Vendrell-Llopis 

In PD, clumps of misfolded alpha-synuclein proteins often accumulate in fragile dopamine-producing neurons in the brain. These clumps, called Lewy bodies, disrupt the function of these neurons and contribute to their breakdown over time. These dopamine neurons are important for movement, so movement symptoms caused by their disruption in PD makes biological sense. 

However, misfolded alpha-synuclein can also form clumps in other neurons in the brain, including those considered to be important for cognition. To date, the association between Lewy bodies and cognitive PD symptoms is not as well understood. Dr. Vendrell-Llopis, from her lab at the University of Alabama at Birmingham, will utilize cutting-edge brain imaging technologies to observe and measure how alpha-synuclein clumps impact learning patterns in mice. She will inject these clumps into neurons within mice, then train those mice to perform a task that uses these specific neurons to receive a reward. 

Some neurons will develop clumps of alpha-synuclein, while others will not. By directly comparing the  activity of neurons with and without alpha-synuclein clumps during this learning task, Dr. Vendrell-Llopis hopes to determine if Lewy bodies are a likely cause of PD-related cognitive symptoms. 

The data collected from these complex studies will allow Dr. Vendrell-Llopis and her team to see which factors, including alpha-synuclein clumping, aging and neuron loss, most affect cognition. She will also perform longer-term studies with these mice, seeing if their learning abilities diminish over time due to progressive alpha-synuclein impacts. 

“The knowledge and tools from this work could make it possible to detect cognitive problems in Parkinson’s disease much earlier, even before standard tests detect any symptoms,” said Dr. Vendrell-Llopis. “Our approach can be used to test new treatments, providing real-time feedback on how therapies impact brain activity and cognitive performance." 

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

2025 Impact Award 

Designing Nanobodies that Stabilize Dysfunctional Proteins in Parkinson’s 

The most common genetic risk factor associated with Parkinson’s disease (PD) lies in the GBA1 gene. Research from the Parkinson’s Foundation genetics study, PD GENEration, has found the GBA1 gene is present in 5-10% of people with the disease. GBA1 provides the instructions to make a protein called glucocerebrosidase (GCase), which plays an important role in the waste recycling compartment of the cell, known as lysosomes.  Variants linked to PD produce unstable or less active versions of GCase.  As a result, cells lose part of their cleanup ability, leading to a buildup of harmful proteins such as alpha-synuclein. 

Wim Versées, PhD, recipient of a Parkinson’s Foundation Impact Award, has discovered a set of small proteins called “nanobodies” that attach to and stabilize these fragile forms of GCase, restoring their functionality in cells where they are needed most.  

Most previous research tried to stabilize GCase using small molecule “chaperones”. These compounds could bind and protect the protein but are often attached to the protein’s active site — the very region needed for its normal function, blocking its activity.  The nanobodies, by contrast, stabilize GCase by binding to a previously unexplored site far away from the active site, preserving its natural role.  

Think of mutant GCase as a fragile vase you want delivered safely to your home. One way to protect it during shipping is to fill it with solid material. That will prevent it from breaking, but once it arrives you can no longer use it to hold flowers. This is what happens when molecules bind the active site. Nanobodies, instead, act by binding or wrapping on the outside of the vase. They keep it intact while still allowing it to hold flowers.  

Supported by the Parkinson’s Foundation Impact Award, Dr. Versées, and his lab at the Flanders Institute for Biotechnology in Belgium, will run a battery of biochemical experiments to hone the design of GCase-stabilizing nanobodies. First, he will use state-of-the-art molecular imaging techniques to see exactly where these nanobodies stick to GCase and how it affects the protein. This information will help Dr. Versées and his team identify which set of nanobodies are the best suited for clinical use and how he can further improve their effectiveness.  

Collaborating with Steven Ballet, PhD, at Vrije Universiteit Brussel, they will also design so-called “peptidomimetics” that are inspired by the nanobodies and have similar GCase-stabilizing features. Since these are much smaller, they can be more easily delivered to the correct cells in the brain, acting as prototypes for future therapeutics. 

Finally, working with Nicoletta Plotegher, PhD, at the University of Padova in Italy, Dr. Versées will test the effectiveness of these nanobodies and peptidomimetics in PD-simulated cells in the lab. Monitoring to what extent the mutant GCase proteins are stabilized and activated with these treatments will validate their potential for future research and their potential as a future treatment. 

Excited by this support, Dr. Versées said “Receiving this award from the Parkinson’s Foundation is both a personal honor and a meaningful endorsement of our research. If successful, this strategy could lead to a new class of molecular chaperones that more effectively target the underlying molecular causes of Parkinson’s, opening new therapeutic avenues for people living with GBA1-associated PD.” 

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

2025 Impact Award 

Building a Toolkit to Study Early-Onset Parkinson’s Genes in Rat Models 

Genetic variants of the genes PRKN and PINK1 are the most common causes of young-onset Parkinson’s disease (PD). These two genes help create proteins, Parkin and Pink1, that maintain healthy mitochondria, the powerhouses of cells. PD-associated variants of these genes lead to impaired mitochondria maintenance and recycling, contributing to the progressive loss of dopamine-producing neurons in the brain. 

Research into PRKN- and PINK1-associated PD has been difficult since mice—the most common animal model for research—with loss of function genetic variants do not exhibit PD-like disease symptoms. This has made it challenging to evaluate therapeutic treatments for PD cases resulting from genetic variants of these genes.  

Kelly Stauch, PhD, recipient of a Parkinson’s Foundation Impact Award, is building out tools so that researchers can better use rats to study mitochondria health in PD. Unlike mice, rats with loss of function PRKN and PINK1 variants develop PD-like neurodegeneration and symptoms, making them more effective animal models for studying these genes.  

“The tools developed as part of this award will aid my PD research as well as others in the field by providing a method to study cell type-specific mitochondria in non-mice models of PD." – Dr. Stauch 

Working out of the University of Nebraska Medical Center in Omaha, Dr. Stauch will utilize a molecular tag that lets her microscopically visualize mitochondria in rat neurons. Co-created with her collaborator Ian Ganley, PhD, this mitochondria tag will establish new data on how Parkin and Pink1 proteins influence mitochondria health and recycling. 

Dr. Stauch will then use a similar mitochondria tag to measure how Parkin and Pink1 disruption affects the function of mitochondria and their recycling in cells. Mitochondria naturally wear out over time, so the ability to disassemble them and make new mitochondria is essential for cell health. Using these tagging tools and looking at PD-related dopamine neurons in rat brains, Dr. Stauch will expand our biological understanding of Pink1 and Parkin-related PD, contributing to future research and treatment development. 

 “This award will allow me to complete this innovative project, which will enable a new approach for studying mitochondria in nigrostriatal dopaminergic neurons in rat models of PD,” said Dr. Stauch. “Further, the tools developed here could be used in other PD rat models as well as adapted to other non-rodent models in the future.” 

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

2025 Stanley Fahn Junior Faculty Award 

Investigating Which Brain Signals Best Guide Adaptive Deep Brain Stimulation 

Deep brain stimulation (DBS) is a promising treatment option for those with Parkinson’s disease (PD) when medications begin to lose their effectiveness. For DBS, electrodes are implanted into the brain that deliver controlled electrical stimulation that counteracts the PD symptoms. 

Most DBS systems are designed to deliver constant, consistent stimulation based on settings set and updated by physicians during checkups. However, a newer version called adaptive DBS (aDBS), recently approved by the FDA for clinical use, monitors brain signals associated with PD symptoms in real time and adjusts stimulation automatically. This ability to auto-adjust stimulation has the potential to enhance DBS efficiency and minimize side effects, improving quality of life for those that use it. 

Lauren Hammer, MD, PhD, recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is working to make aDBS even more effective by determining which types of brain signals offer the best information on how to adjust stimulation in response to symptoms. Current aDBS technology monitors low-frequency brain waves called “beta” signals, but Dr. Hammer believes that higher frequency “entrained-gamma” signals may be better for predicting and controlling PD symptoms. 

 “This research aims to advance deep brain stimulation for Parkinson’s disease by identifying the most effective neural signal to guide adaptive DBS,” said Dr. Hammer. 

From her lab at the University of Pennsylvania, a Parkinson’s Foundation Center of Excellence, Dr. Hammer will first run an in-laboratory assessment where people with PD perform various movement tasks while their brain signals are monitored. This will provide data as to which type of signal — beta or entrained-gamma — offers a more accurate reflection for when PD symptoms like involuntary movements are occurring. 

Dr. Hammer will then take a small group of people with DBS for their PD and upgrade them to aDBS for an at-home study. After participants are programmed for aDBS stimulation using both beta signals and entrained-gamma signals, they will switch weekly between these settings, recording how well their symptoms are controlled at home.   

At the end of the trial, Dr. Hammer and her team will have data to suggest which signal type guided the best aDBS experience for different types of people with PD.  

When asked what this support means to her and her research goals, Dr. Hammer said “Receiving this award is an incredible honor and an important milestone in my journey to improve the lives of people with Parkinson’s disease. This research could support expanding the set of neural signals used for clinical aDBS, enabling more effective and personalized treatment.” 

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