Identification of diagnostic and prognostic biomarkers of PD using a multiplex proteomics approach
Given the complexity of Parkinson's disease (PD), achieving acceptable diagnostic and prognostic accuracy will require the support of a panel of diverse biomarkers. We used Proximity extension assays to measure a panel of 92 proteins in CSF of 120 newly diagnosed PD patients and 45 control subj...
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| Published in | Neurobiology of disease Vol. 186; p. 106281 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier Inc
01.10.2023
Elsevier |
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| Abstract | Given the complexity of Parkinson's disease (PD), achieving acceptable diagnostic and prognostic accuracy will require the support of a panel of diverse biomarkers. We used Proximity extension assays to measure a panel of 92 proteins in CSF of 120 newly diagnosed PD patients and 45 control subjects without neurological disease. From 75 proteins detectable in the CSF of >90% of the subjects, regularized regression analysis identified four proteins (β-NGF, CD38, tau and NCAN) as downregulated in newly diagnosed PD patients (age at diagnosis 67.2 ± 9.4 years) compared to controls (age 65.4 ± 10.9 years). Higher tau (β −0.82 transformed MMSE points/year, 95% CI −1.37 to −0.27, P = 0.005) was also linked to faster cognitive decline over the first ten years after PD diagnosis. These findings provide insights into multiple aspects of PD pathophysiology and may serve as the foundation for identifying new biomarkers and therapeutic targets.
•Proximity extension assays enable high-throughput, multiplex analysis of proteins•PEA detected 4 neurology-related proteins dysregulated in CSF from patients with PD•β-NGF, CD38, Tau and NCAN were all downregulated in newly diagnosed PD patients•Higher Tau protein was linked to faster cognitive decline in PD•The proteins identified reflect broader biology than do the classic PD biomarkers |
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| AbstractList | Given the complexity of Parkinson's disease (PD), achieving acceptable diagnostic and prognostic accuracy will require the support of a panel of diverse biomarkers. We used Proximity extension assays to measure a panel of 92 proteins in CSF of 120 newly diagnosed PD patients and 45 control subjects without neurological disease. From 75 proteins detectable in the CSF of >90% of the subjects, regularized regression analysis identified four proteins (β-NGF, CD38, tau and NCAN) as downregulated in newly diagnosed PD patients (age at diagnosis 67.2 ± 9.4 years) compared to controls (age 65.4 ± 10.9 years). Higher tau (β −0.82 transformed MMSE points/year, 95% CI −1.37 to −0.27, P = 0.005) was also linked to faster cognitive decline over the first ten years after PD diagnosis. These findings provide insights into multiple aspects of PD pathophysiology and may serve as the foundation for identifying new biomarkers and therapeutic targets. Given the complexity of Parkinson's disease (PD), achieving acceptable diagnostic and prognostic accuracy will require the support of a panel of diverse biomarkers. We used Proximity extension assays to measure a panel of 92 proteins in CSF of 120 newly diagnosed PD patients and 45 control subjects without neurological disease. From 75 proteins detectable in the CSF of >90% of the subjects, regularized regression analysis identified four proteins (β-NGF, CD38, tau and NCAN) as downregulated in newly diagnosed PD patients (age at diagnosis 67.2 ± 9.4 years) compared to controls (age 65.4 ± 10.9 years). Higher tau (β −0.82 transformed MMSE points/year, 95% CI −1.37 to −0.27, P = 0.005) was also linked to faster cognitive decline over the first ten years after PD diagnosis. These findings provide insights into multiple aspects of PD pathophysiology and may serve as the foundation for identifying new biomarkers and therapeutic targets. •Proximity extension assays enable high-throughput, multiplex analysis of proteins•PEA detected 4 neurology-related proteins dysregulated in CSF from patients with PD•β-NGF, CD38, Tau and NCAN were all downregulated in newly diagnosed PD patients•Higher Tau protein was linked to faster cognitive decline in PD•The proteins identified reflect broader biology than do the classic PD biomarkers |
| ArticleNumber | 106281 |
| Author | Maple-Grødem, Jodi Ushakova, Anastasia Pedersen, Kenn Freddy Alves, Guido Tysnes, Ole-Bjørn Lange, Johannes |
| Author_xml | – sequence: 1 givenname: Jodi surname: Maple-Grødem fullname: Maple-Grødem, Jodi email: jodi.maple@uis.no, jodi.maple.grodem@sus.no organization: Centre for Movement Disorders, Centre for Brain Health, Stavanger University Hospital, Stavanger, Norway – sequence: 2 givenname: Anastasia surname: Ushakova fullname: Ushakova, Anastasia email: anastasia.ushakova@sus.no organization: Section of Biostatistics, Department of Research, Stavanger University Hospital, Stavanger, Norway – sequence: 3 givenname: Kenn Freddy surname: Pedersen fullname: Pedersen, Kenn Freddy email: kenn.freddy.pedersen@sus.no organization: Centre for Movement Disorders, Centre for Brain Health, Stavanger University Hospital, Stavanger, Norway – sequence: 4 givenname: Ole-Bjørn surname: Tysnes fullname: Tysnes, Ole-Bjørn email: ole-bjorn.tysnes@helse-bergen.no organization: Department of Neurology, Haukeland University Hospital, Bergen, Norway – sequence: 5 givenname: Guido surname: Alves fullname: Alves, Guido email: guido.alves@sus.no organization: Centre for Movement Disorders, Centre for Brain Health, Stavanger University Hospital, Stavanger, Norway – sequence: 6 givenname: Johannes surname: Lange fullname: Lange, Johannes email: johannes.lange@sus.no organization: Centre for Movement Disorders, Centre for Brain Health, Stavanger University Hospital, Stavanger, Norway |
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| CitedBy_id | crossref_primary_10_1016_j_compbiomed_2024_108200 crossref_primary_10_3389_fbioe_2024_1415527 |
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| Keywords | Biomarkers Parkinson's disease Proximity extension assay CSF |
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