Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders

Camilla Christina Pedersen; Anastasia Ushakova; Ragnhild Eide Skogseth; Guido Alves; Ole-Bjørn Tysnes; Dag Aarsland; Johannes Lange; Jodi Maple-Grødem

doi:10.1212/NXI.0000000000200132

Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders

Neurol Neuroimmunol Neuroinflamm. 2023 May 31;10(4):e200132. doi: 10.1212/NXI.0000000000200132. Print 2023 Jul.

Authors

Camilla Christina Pedersen¹, Anastasia Ushakova¹, Ragnhild Eide Skogseth¹, Guido Alves¹, Ole-Bjørn Tysnes¹, Dag Aarsland¹, Johannes Lange¹, Jodi Maple-Grødem²

Affiliations

¹ From the The Norwegian Centre for Movement Disorders (C.C.P., G.A., J.L., J.M.-G.), Stavanger University Hospital; Department of Chemistry, Bioscience and Environmental Engineering (C.C.P., G.A., J.L., J.M.-G.), University of Stavanger; Section of Biostatistics (A.U.), Department of Research, Stavanger University Hospital; Department of Geriatric Medicine (R.E.S.), Haraldsplass Deaconess Hospital, Bergen; Department of Clinical Medicine (R.E.S., O.-B.T.), University of Bergen; Department of Neurology (G.A.), Stavanger University Hospital; Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen; Centre for Age-Related Medicine (D.A.), Stavanger University Hospital, Norway; and Department of Old Age Psychiatry (D.A.), Institute of Psychiatry, Psychology, and Neuroscience, King's College London, United Kingdom.
² From the The Norwegian Centre for Movement Disorders (C.C.P., G.A., J.L., J.M.-G.), Stavanger University Hospital; Department of Chemistry, Bioscience and Environmental Engineering (C.C.P., G.A., J.L., J.M.-G.), University of Stavanger; Section of Biostatistics (A.U.), Department of Research, Stavanger University Hospital; Department of Geriatric Medicine (R.E.S.), Haraldsplass Deaconess Hospital, Bergen; Department of Clinical Medicine (R.E.S., O.-B.T.), University of Bergen; Department of Neurology (G.A.), Stavanger University Hospital; Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen; Centre for Age-Related Medicine (D.A.), Stavanger University Hospital, Norway; and Department of Old Age Psychiatry (D.A.), Institute of Psychiatry, Psychology, and Neuroscience, King's College London, United Kingdom. jodi.maple@uis.no.

Abstract

Background and objectives: Neuroinflammation contributes to Parkinson disease (PD) pathology, and inflammatory biomarkers may aid in PD diagnosis. Proximity extension assay (PEA) technology is a promising method for multiplex analysis of inflammatory markers. Neuroinflammation also plays a role in related neurodegenerative diseases, such as dementia with Lewy bodies (DLB) and Alzheimer disease (AD). The aim of this work was to assess the value of inflammatory biomarkers in newly diagnosed patients with PD and in patients with DLB and AD.

Methods: Patients from the Norwegian ParkWest and Dementia Study of Western Norway longitudinal cohorts (PD, n = 120; DLB, n = 15; AD, n = 27) and 44 normal controls were included in this study. A PEA inflammation panel of 92 biomarkers was measured in the CSF. Disease-associated biomarkers were identified using elastic net (EN) analysis. We assessed the discriminatory power of disease-associated biomarkers using receiver operating characteristic (ROC) curve analysis and estimated the optimism-adjusted area under the curve (AUC) using the bootstrapping method.

Results: EN analysis identified 9 PEA inflammatory biomarkers (ADA, CCL23, CD5, CD8A, CDCP1, FGF-19, IL-18R1, IL-6, and MCP-2) associated with PD. Seven of the 9 biomarkers were included in a diagnostic panel, which was able to discriminate between those with PD and controls (optimism-adjusted AUC 0.82). Our 7-biomarker PD panel was also able to distinguish PD from DLB and from AD. In addition, 4 inflammatory biomarkers were associated with AD and included in a panel, which could distinguish those with AD from controls (optimism-adjusted AUC 0.87). Our 4-biomarker AD panel was also able to distinguish AD from DLB and from PD.

Discussion: In our exploratory study, we identified a 7-biomarker panel for PD and a 4-biomarker panel for AD. Our findings indicate potential inflammation-related biomarker candidates that could contribute toward PD-specific and AD-specific diagnostic panels, which should be further explored in other larger cohorts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnosis
Antigens, Neoplasm
Biomarkers
Cell Adhesion Molecules
Humans
Lewy Body Disease* / diagnosis
Neurodegenerative Diseases* / diagnosis
Neuroinflammatory Diseases
Parkinson Disease* / complications
Parkinson Disease* / diagnosis
tau Proteins

Substances

tau Proteins
Biomarkers
CDCP1 protein, human
Antigens, Neoplasm
Cell Adhesion Molecules