CSF α-synuclein aggregate information cannot (yet) predict Parkinson’s disease progression rates
Fujita Health University & Harvard University Collaboration Sheds New Light on Parkinson’s Disease Biomarkers
Researchers from Fujita Health University have collaborated for years with Harvard University to advance the understanding of Parkinson’s disease. Now, they have gained new insight into the role of cerebrospinal fluid (CSF) α-synuclein aggregates in Parkinson’s disease (PD). The joint study, published in eBioMedicine (a journal of The Lancet family), explored whether measuring α-synuclein seeding activity in CSF could predict the pace of disease progression. Seeding activity refers to the process by which misfolded α-synuclein recruits normal protein and templates the formation of pathogenic aggregates.
Led by Dr. Xiqun Chen (Massachusetts General Hospital, Harvard Medical School) and involving Fujita Health University alongside leading U.S. research institutions including Yale University, the team analyzed up to seven years of follow-up data from 564 participants in the Parkinson’s Progression Markers Initiative (PPMI). Using data from highly sensitive α-synuclein seed amplification assays(SAAs), they confirmed that α-synuclein aggregates were detectable in most PD patients—though less often in those with an LRRK2 mutation—supporting the well-established association of α-synuclein aggregation with PD pathology.
Crucially, however, the study found that the baseline presence and estimated abundance of CSF α-synuclein aggregates were not significantly linked with the rate of decline in motor function, cognition, or dopamine transporter imaging measures.
“While α-synuclein SAAs are a powerful diagnostic tool, our findings suggest that a single measurement at diagnosis is not sufficient to forecast the future course of Parkinson’s disease,” said Professor Hirohisa Watanabe of Fujita Health University.
The results highlight the complexity of PD progression and the challenge of interpreting what SAA-detected aggregates signify for prognosis. They underscore the need for longitudinal studies that track α-synuclein seeding activity over time, and for multimodal approaches that combine SAAs with complementary fluid and imaging biomarkers.
“Our collaboration with Dr. Chen’s team shows the value of large, international partnerships in tackling these challenging questions,” Watanabe added.
The researchers stress that their findings do not diminish the importance of α-synuclein biology in PD, but instead point to the necessity of multi-modal, longitudinal biomarker strategies to fully capture disease heterogeneity and progression.
Researchers from Fujita Health University have collaborated for years with Harvard University to advance the understanding of Parkinson’s disease. Now, they have gained new insight into the role of cerebrospinal fluid (CSF) α-synuclein aggregates in Parkinson’s disease (PD). The joint study, published in eBioMedicine (a journal of The Lancet family), explored whether measuring α-synuclein seeding activity in CSF could predict the pace of disease progression. Seeding activity refers to the process by which misfolded α-synuclein recruits normal protein and templates the formation of pathogenic aggregates.
Led by Dr. Xiqun Chen (Massachusetts General Hospital, Harvard Medical School) and involving Fujita Health University alongside leading U.S. research institutions including Yale University, the team analyzed up to seven years of follow-up data from 564 participants in the Parkinson’s Progression Markers Initiative (PPMI). Using data from highly sensitive α-synuclein seed amplification assays(SAAs), they confirmed that α-synuclein aggregates were detectable in most PD patients—though less often in those with an LRRK2 mutation—supporting the well-established association of α-synuclein aggregation with PD pathology.
Crucially, however, the study found that the baseline presence and estimated abundance of CSF α-synuclein aggregates were not significantly linked with the rate of decline in motor function, cognition, or dopamine transporter imaging measures.
“While α-synuclein SAAs are a powerful diagnostic tool, our findings suggest that a single measurement at diagnosis is not sufficient to forecast the future course of Parkinson’s disease,” said Professor Hirohisa Watanabe of Fujita Health University.
The results highlight the complexity of PD progression and the challenge of interpreting what SAA-detected aggregates signify for prognosis. They underscore the need for longitudinal studies that track α-synuclein seeding activity over time, and for multimodal approaches that combine SAAs with complementary fluid and imaging biomarkers.
“Our collaboration with Dr. Chen’s team shows the value of large, international partnerships in tackling these challenging questions,” Watanabe added.
The researchers stress that their findings do not diminish the importance of α-synuclein biology in PD, but instead point to the necessity of multi-modal, longitudinal biomarker strategies to fully capture disease heterogeneity and progression.