The Parkinson’s Foundation is proud to invest in research initiatives that aim to improve our understanding of Parkinson’s disease (PD), work toward new treatments and, ultimately, a cure.
Two of our current researchers are investigating what happens when a protein integral to the development of Parkinson’s — called alpha-synuclein — begins to accumulate in the brain, and whether this early accumulation can lead to earlier diagnosis of Parkinson’s. Both studies could lead to important breakthroughs in diagnosing PD and understanding how PD develops and progresses.
Sarah Shahmoradian, PhD: Learning About Early-Stage Accumulation of Alpha-Synuclein in the Parkinson’s Brain
Sarah Shahmoradian, PhD, of the University of Texas Southwestern Medical Center, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study early-stage build-up of a protein called alpha-synuclein in the brain.
In Parkinson’s, the alpha-synuclein protein misfolds into an abnormal shape, causing the protein to clump together. These protein deposits have been linked to the loss of brain cells. In addition, alpha-synuclein deposits have been correlated with cognitive decline in PD.
Prior research has largely focused on the late stages of alpha-synuclein accumulation. However, much is still not known about the critical early events that cause a single abnormal alpha-synuclein molecule to recruit and transform additional molecules to become toxic. This leads to build-up and spreading to other brain cells.
Dr. Shahmoradian will apply state-of-the-art, high-resolution imaging techniques to uncover the molecular structure of alpha-synuclein within the brain cells, and to study how alpha-synuclein contributes to the disease process in Parkinson’s. This research will define where and how alpha-synuclein buildup first occurs within human brain cells.
“Results from these studies will fundamentally advance our understanding of how Parkinson’s disease develops. They could thereby inform on novel therapeutic strategies.”
Giovanni Bellomo, PhD: Creating A Diagnostic Test Could Detect Parkinson’s Earlier
Giovanni Bellomo, PhD, of the University of Perugia in Italy, received a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists to improve the usefulness of a group of testing techniques called seed amplification assays (SAAs) in the early diagnosis of Parkinson’s disease.
Currently, there is no single test to diagnose PD, and movement disorders specialists often rely on the presence of movement symptoms to make a diagnosis. However, by the time someone with PD shows symptoms, the disease is already past its early phase. Early detection would allow earlier disease-modifying treatment, which could potentially benefit people with Parkinson’s.
One of the earliest known changes that occurs in brains affected with PD is the emergence of alpha-synuclein deposits. Tests like the seed amplification assays are used to detect a biomarker (a biological molecule that is a sign of disease). Having a biomarker for Parkinson’s could lead to earlier diagnosis and can improve outcomes for people living with PD.
Seed amplification assays have been successfully used to detect alpha-synuclein pathological changes in the cerebrospinal fluid (CSF) of people with Parkinson’s. However, several factors limit their use in clinical practice. To overcome the existing limitations, Dr. Bellomo will study whether the olfactory mucosa (i.e., nasal cells) can be used in SAAs. Collecting these samples is easily achieved by using a swab to scrape small amounts of olfactory mucosa from inside the nose. This non-intrusive test would represent a breakthrough in Parkinson's diagnosis, as no such test currently exists.
Second, Dr. Bellomo also aims to improve current CSF SAAs by making them capable of estimating the amount of disease-causing alpha-synuclein present in CSF samples. This is a key step toward testing treatments against pathological forms of alpha-synuclein.
“This research will improve the usefulness of SAAs in obtaining a specific and early diagnosis of PD. This is crucial for properly planning a treatment approach and including people with PD in clinical trials.”
Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.