PT  - JOURNAL ARTICLE
AU  - Camilla Christina Pedersen
AU  - Anastasia Ushakova
AU  - Ragnhild Eide Skogseth
AU  - Guido Alves
AU  - Ole-Bjørn Tysnes
AU  - Dag Aarsland
AU  - Johannes Lange
AU  - Jodi Maple-Grødem
TI  - Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders
AID  - 10.1212/NXI.0000000000200132
DP  - 2023 Jul 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200132
VI  - 10
IP  - 4
4099  - http://nn.neurology.org/content/10/4/e200132.short
4100  - http://nn.neurology.org/content/10/4/e200132.full
SO  - Neurol Neuroimmunol Neuroinflamm2023 Jul 01; 10
AB  - 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.AD=Alzheimer disease; APS=atypical parkinsonian syndromes; AUC=area under the curve; DLB=dementia with Lewy bodies; EN=elastic net; LLOD=lower limit of detection; MMSE=Mini-Mental State Examination; NPX=normalized protein expression; PD=Parkinson disease; PEA=proximity extension assays; ROC=receiver operating characteristic; UPDRS=Unified Parkinson Disease Rating Scale; VIFs=variance inflation factors