Parkinson's and Alzheimer's may share more biology than once thought. MJFF Chief Scientist Mark Frasier explains what researchers are learning and why it matters.
For most people, Parkinson's disease and Alzheimer's disease are thought of as two very different conditions. Parkinson's primarily affects movement, while Alzheimer's is best known for causing memory loss and changes in thinking.
Increasingly, however, researchers are discovering that these diseases may have more in common than previously thought.
New tools that can detect the biology of disease — from blood biomarkers to advancing imaging and diagnostic approaches — are revealing that many people living with Parkinson's also have biological changes associated with Alzheimer's, while many people living with Alzheimer's also have Parkinson's-related pathology. This overlap, known as mixed pathology (or co-pathology) is helping researchers better understand why symptoms progress differently from person to person and why future treatments may need to be tailored to an individual's unique biology.
Earlier this year, Science magazine explored this emerging field in a feature on mixed pathology across neurodegenerative diseases, including insights from MJFF Chief Scientist Mark Frasier, PhD. Recent headlines have highlighted promising blood biomarkers for Alzheimer's disease, such as p-tau217, that may help detect disease biology years before symptoms appear. These advances are giving researchers a much clearer picture of how neurodegenerative diseases develop and how they may be more closely connected than we once realized.
We asked Dr. Frasier to expand on some of the themes from the Science article and explain what these discoveries mean for people living with Parkinson's.
MJFF: Researchers are increasingly talking about "mixed pathology." What does that mean, and why is it becoming such an important focus?
Mark Frasier: Mixed pathology means that many people living with a neurodegenerative disease don't have just one disease-related protein in their brain.
For example, someone with Parkinson's may have alpha-synuclein, the hallmark protein associated with Parkinson's. But they may also have amyloid or tau, which are proteins more commonly associated with Alzheimer's disease. Likewise, many people living with Alzheimer's also have alpha-synuclein pathology. Current research suggests this may occur in an estimated 30–50% of people with Alzheimer's disease.
Scientists have actually observed this for years through autopsy studies. What's changed is that we're finally developing tools that allow us to detect these pathologies in living people, often much earlier in the disease process.
That changes how we think about neurodegenerative disease. Instead of viewing Parkinson's and Alzheimer's as completely separate conditions, we're beginning to understand how overlapping biology may influence symptoms, progression and, ultimately, treatment.
MJFF: Biomarkers are tools that can detect the earliest biological signs of disease in living people. Why are better biomarkers so important to understanding mixed pathology, and how could they change clinical trials?
MF: Biomarkers are tools that help us understand what's happening inside the brain while someone is living. Researchers are looking throughout the body — including blood, spinal fluid and skin — for biological clues that reflect what's happening in the brain. If we want to treat disease, we first have to be able to measure it.
Better biomarkers help researchers enroll the right participants, ask better scientific questions, and design smarter clinical trials.
One of the best examples comes from Alzheimer's disease. Early clinical trials of anti-amyloid therapies included people who, it turned out, didn't actually have significant amyloid in their brains. Once researchers developed biomarkers to confirm amyloid before enrollment, those trials became much more informative.
Parkinson's research is now beginning to follow that same path. For example, researchers are using an Alzheimer's blood biomarker called p-tau217 in Parkinson's studies to better understand why some people develop cognitive impairment while others do not. These findings are helping researchers understand how Alzheimer's-related pathology may influence Parkinson's disease.
At the same time, researchers are working to develop Parkinson's-specific blood biomarkers for alpha-synuclein. Today, measuring alpha-synuclein largely requires a spinal tap, but a simple blood test could make research more accessible, improve clinical trial enrollment and ultimately help accelerate development of more personalized treatments.
MJFF: What could this ultimately mean for people living with Parkinson's?
MF: The long-term goal is precision medicine.
Instead of treating Parkinson's as though everyone experiences the disease the same way, biomarkers could help doctors understand the biology driving each person's disease and eventually tailor treatments accordingly.
Along the way, these tools could also provide greater confidence in diagnosis and help people better understand what to expect over time. As researchers continue to identify disease biology earlier, biomarkers may also help people participate in research sooner and, eventually, receive treatments before significant nerve cell loss has occurred.
That's really where we hope the field is headed - matching the right treatment to the right person at the right time.
MJFF: MJFF is supporting mixed pathology research in many different ways — from biomarker development to collaborations across the field. How do those efforts fit together?
MF: As new biomarker tools emerge, we're learning that many neurodegenerative diseases share more biology than we once appreciated. That creates opportunities to learn across diseases rather than studying each one in isolation. Each of MJFF's programs tackles a different piece of the puzzle.
Through partnerships like our collaboration with the Alzheimer's Drug Discovery Foundation, we're helping accelerate development of minimally invasive biomarkers, which are tests that can detect disease biology using samples like blood or skin instead of more invasive procedures such as spinal taps.
Through the Foundation’s longstanding longitudinal study, the Parkinson's Precision Medicine Initiative, we're using those tools to understand when these pathologies appear and how they influence disease progression.
The Collaborative Research Network, which is supported by the Aligning Science Across Parkinson's initiative in partnership with MJFF, is helping researchers understand how these proteins interact at the cellular level, while our Endotypes Program is bringing together data to better understand the spectrum of neurodegenerative diseases.
Together, those efforts connect the dots from developing better tools, to understanding disease biology, to improving treatments.
MJFF: Looking ahead, what gives you the most hope?
MF: I'm encouraged by how quickly the field is moving. Every new biomarker allows researchers to ask better questions and better understand disease biology. We're learning from advances in Alzheimer's research rather than starting from scratch and vice versa. Progress in one neurodegenerative disease is increasingly helping accelerate progress in another.
Ultimately, I think these advances are bringing us closer to precision medicine. If we can identify the biology driving a person's disease earlier and understand how multiple pathologies interact, we'll be much better positioned to develop treatments that are tailored to the individual. That's ultimately what we're working toward.
As researchers work toward earlier detection and more personalized treatments, people with Parkinson's and their loved ones remain our most important partners. Their participation in research is helping turn discoveries like these into tomorrow's treatments. Learn more about getting involved in Parkinson's research: https://www.michaeljfox.org/your-role-parkinsons-research.
"If we want to treat disease, we first have to be able to measure it."