High-Throughput CSF Proteomics and Machine Learning to Identify Proteomic Signatures for Parkinson Disease Development and Progression
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- Kazuto Tsukita
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Haruhi Sakamaki-Tsukita
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Sergio Kaiser
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Luqing Zhang
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Mirko Messa
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Pablo Serrano-Fernandez
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
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- Ryosuke Takahashi
- From the Department of Neurology (K.T., H.S.-T., R.T.), Graduate School of Medicine, Kyoto University; Advanced Comprehensive Research Organization (K.T.), Teikyo University, Itabashi; Division of Sleep Medicine (K.T.), Kansai Electric Power Medical Research Institute, Osaka, Japan; Translational Medicine Department (S.K., P.S.-F.), Novartis Institutes for Biomedical Research, Basel, Switzerland; and Cardiovascular and Metabolism Department (L.Z.), and Neuroscience Department (M.M.), Novartis...
書誌事項
- 公開日
- 2023-10-03
- 資源種別
- journal article
- DOI
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- 10.1212/wnl.0000000000207725
- 公開者
- Ovid Technologies (Wolters Kluwer Health)
この論文をさがす
説明
This study aimed to identify CSF proteomic signatures characteristic of Parkinson disease (PD) and evaluate their clinical utility.This observational study used data from the Parkinson's Progression Markers Initiative (PPMI), which enrolled patients with PD, healthy controls (HCs), and non-PD participants carryingData from 279 patients with nongenetic PD (mean ± SD, age 62.0 ± 9.6 years; male 67.7%) and 141 HCs (age 60.5 ± 11.9 years; male 64.5%) were used for PD-ProS derivation. From 23 DEPs, LASSO determined weights of 14 DEPs for the PD-ProS (area under the curve [AUC] 0.83, 95% CI 0.78-0.87), validated in an independent internal validation cohort of 71 patients with nongenetic PD and 35 HCs (AUC 0.81, 95% CI 0.73-0.90). In the LCC, only 5 of the 14 DEPs were also measured. Notably, these 5 DEPs still distinguished 34 patients with nongenetic PD from 31 HCs with the same weights (AUC 0.75, 95% CI 0.63-0.87). Furthermore, the PD-ProS distinguished 258 patients with genetic PD from 365 genetic prodromals. Finally, regardless of genetic status, the PD-ProS independently predicted both cognitive and motor decline in PD (dementia, adjusted hazard ratio in the highest quintile [aHR-Q5] 2.8 [95% CI 1.6-5.0]; Hoehn and Yahr stage IV, aHR-Q5 2.1 [95% CI 1.1-4.0]).By integrating high-throughput proteomics with machine learning, we identified PD-associated CSF proteomic signatures crucial for PD development and progression.ClinicalTrials.gov (NCT01176565). A link to the trial registry page is clinicaltrials.gov/ct2/show/NCT01141023.This study provides Class II evidence that the CSF proteome contains clinically important information regarding the development and progression of Parkinson disease that can be deciphered by a combination of high-throughput proteomics and machine learning.
収録刊行物
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- Neurology
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Neurology 101 (14), 2023-10-03
Ovid Technologies (Wolters Kluwer Health)
