Plasma extracellular vesicle tau, β-amyloid, and α-synuclein and the progression of Parkinson’s disease: a follow-up study
Bibliographic record
Abstract
Background: Plasma extracellular vesicle (EV) contents are promising biomarkers of Parkinson's disease (PD). The pathognomonic proteins of PD, including α-synuclein, tau, and β-amyloid, are altered in people with PD (PwP) and are associated with clinical presentation in previous cross-sectional studies. However, the dynamic changes in these plasma EV proteins in PwP and their correlation with clinical progression remain unclear. Objective: We investigated the dynamic changes in plasma EV α-synuclein, tau, and β-amyloid and their correlation with/prediction of clinical progression in PwP. Design: A cohort study. Methods: In total, 103 PwP and 37 healthy controls (HCs) completed baseline assessment and 1-year follow-up. Clinical assessments included Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess α-synuclein, tau, and β-amyloid 1-42 (Aβ1-42) levels within the EVs. Results: Compared with HCs, significant differences were noted in the annual changes in all three EV pathognomonic proteins in PwP. Although the absolute changes in plasma EV pathognomonic proteins did not significantly correlate with clinical changes, PwP with elevated baseline plasma EV tau (upper-half) levels demonstrated significantly greater decline in motor and cognition, and increased plasma EV α-synuclein levels were associated with postural instability and the gait disturbance motor subtype. For PwP with elevated levels of all three biomarkers, clinical deterioration was significant, as indicated by UPDRS-II scores, postural instability and gait disturbance subscores of UPDRS-III, and MMSE score. Conclusion: The combination of plasma EV α-synuclein, tau, and Aβ1-42 may identify PwP with a high risk of deterioration. Our findings can elucidate the interaction between these pathognomonic proteins, and they may serve as treatment response markers and can be applied in treatment approaches for disease modification.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".