Cerebrospinal Fluid Levels of Kininogen‐1 Indicate Early Cognitive Impairment in Parkinson's Disease

Abstract

Background: Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date. Objectives: The aim of this study was to investigate CSF markers associated with cognition in early PD. Methods: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination. Results: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (<90). Of 14 proteins in CSF that differed in levels between groups, increased kininogen-1, validated with several antibodies, was independently associated with lower Repeatable Battery for the Assessment of the Neuropsychological Status and Montreal Cognitive Assessment scores after adjustment for confounders. Conclusions: Kininogen-1 levels in CSF may serve as a marker of cognitive impairment in PD.

Multi-Omics Interdisciplinary Research Integration to Accelerate Dementia Biomarker Development (MIRIADE)

“…The panel of proteins was further developed and narrowed in succeeding studies on various neurodegenerative disorders to investigate disease specificity. These studies focused on AD ( 15 , 16 ), PD ( 17 ), and FTD ( 18 , 19 ) amyotrophic lateral sclerosis (ALS) ( 20 )) and corticobasal degeneration (CBD) ( 21 ). In addition, one study investigated the associations of the selected panel proteins with the conventional CSF biomarkers for AD pathology on an asymptomatic cohort of asymptomatic 70-year-old individuals ( 22 ).…”

Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy

“…There have been limitations in the analysis of other omics data, except for metabolites, from CSF samples due to technical issues. However, recently, proteome analysis using LC-MS/MS [108] and antibody array [109] have been developed, and quantitative PCR for microRNAs can determine the levels of microRNAs [13]. Such analytical improvement enables researchers to overcome limitations and analyze clinical symptoms comprehensively.…”

Mass Spectrometry-Based Analysis of Serum N-Glycosylation Changes in Patients with Parkinson’s Disease

“…It should be noted that instead of listing all identified glycosylation in control and PD sera, we only presented the contrast changes (site-specific glycosylation uniquely identified in PD patients’ sera). Some of the proteins identified in the analysis of intact glycopeptides are associated with PD (Table ), including ceruloplasmin (P00450), haptoglobin (P00738), kininogen-1 (P01042), complement factor H (P08603), and clusterin (P10909) . Ceruloplasmin has ferroxidase activity and is involved in brain iron metabolism.…”

“…However, the role of kininogen-1 in PD is still unclear. 32 Complement activation, a key event in neuroinflammation, has been reported in PD 37 and can be inhibited by complement factor H. Clusterin is an extracellular chaperone protein that can suppress the toxicity of α-synuclein oligomers. 38 Aberrant glycosylation may affect protein−protein interactions, leading to altered signaling pathways and ultimately disease pathogenesis.…”