Parkinson’s Disease Isn’t One-Size-Fits-All: Scientists Discover Distinct Disease Pathways with Major Treatment Implications
For patients and their Parkinson’s disease care team, understanding the progression of the disease is key to managing expectations and treatment. A groundbreaking new study published in Science Advances reveals that Parkinson’s may not be a single disease with a uniform path, but rather a condition with at least two distinct biological trajectories. This discovery could fundamentally change how we approach treatment and manage Parkinson’s disease and life expectancy.
The Two Faces of a Key Protein
At the heart of Parkinson’s is the accumulation of a misfolded protein called alpha-synuclein (α-Syn). However, this protein can form different types of clumps: large aggregates (Lewy bodies, or LA) and smaller, soluble aggregates (SA).
Using a non-human primate model—the closest analog to humans—French researchers from the University of Bordeaux injected these two different types of α-Syn aggregates into the brains of baboons. While both types ultimately led to the loss of dopamine-producing neurons after two years, the path to that damage was strikingly different.
- LA (Large Aggregates) Pathway: This group showed a “fast-burn” trajectory. Neurodegeneration began earlier, at the 6- and 12-month marks, and involved more widespread brain changes, including synaptic disruption and mitochondrial dysfunction.
- SA (Small Aggregates) Pathway: This group followed a “slow-burn” path. Damage accumulated more slowly, with a primary focus on mitochondrial health.
Implications for Patients and a Parkinson’s Disease Care Team
This finding is crucial for personalizing treatment. A one-size-fits-all approach may be why many therapies fail. For instance, an immunotherapy designed to clear large Lewy bodies might be more effective for a patient on the LA trajectory, while a therapy targeting mitochondrial health could be better for someone on the SA path.
This nuanced understanding can help a caregiver for Parkinson’s disease with dementia better anticipate the specific challenges their loved one might face, whether they relate to movement, cognition, or mood. It also highlights the importance of a comprehensive Parkinson’s disease care team that can address the multifaceted nature of the disease.
A Hopeful Outlook and Proactive Management
This research opens the door to biologically defining subtypes of Parkinson’s, which can lead to more targeted and effective treatments. While managing Parkinson’s disease and life expectancy is a primary concern, understanding these subtypes could lead to interventions that significantly slow progression, improving both quality and length of life.
In the meantime, proactive activities remain beneficial. For example, research has shown that exercise like swim for Parkinson’s disease can help maintain mobility and balance. The gentle, resistance-based nature of water makes activities like swim for Parkinson’s disease an excellent low-impact option for many patients.
The Bottom Line
Parkinson’s disease is more complex than previously thought. By recognizing its different pathways, we can move toward a future of precision medicine, where treatments are tailored to the individual’s specific biological version of the disease. This brings new hope for more effective management and outcomes.
Source:
Kinet R, Bourdenx M, Dovero S, et al. Differential pathological dynamics triggered by distinct Parkinson patient–derived α-synuclein extracts in nonhuman primates. Science Advances. 2025;11(25):eadu6050.
This article is for informational purposes only and does not constitute medical advice. Please consult with a healthcare professional for any health concerns.