Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Combined with Magnetic Beads for Detecting Serum Protein Biomarkers in Parkinson’s Disease

Abstract

Background: Biomarkers for neurodegenerative diseases are essential to facilitate disease diagnosis. Application of proteomics has greatly hastened the search for novel biomarkers. In this study, new potential biomarkers were discovered, and a diagnostic pattern was established for idiopathic Parkinson’s disease (PD) by using proteomic technology. Methods: Serum proteins from PD patients and controls were captured by magnetic bead-based weak cation exchange. The molecular weight of the proteins in bead-binding fraction was detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Biomarker Wizard 3.1 and Biomarker Patterns Software were used for data analysis and constructing a model of biomarkers. A blinded testing set was used to validate the model. Results: A total of 17 discriminating m/z peaks related to PD were identified. The model based on the 5 biomarkers generated an excellent separation between PD and healthy controls with 98.36% for the sensitivity and 83.05% for the specificity. Blind test data demonstrated the model could recognize patients with PD with a sensitivity of 85.0% and a specificity of 70.0%. Conclusions: The preliminary data suggested a potential application of MALDI-TOF-MS combined with magnetic beads. The model comprising 5 promising biomarkers can differentiate individuals with PD and the healthy subjects precisely.

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

“…Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), other protein species have been identified that are differentially expressed between PD and controls, [84][85][86] and recent analysis of proteins captured by magnetic bead-based weak cation exchange followed by MALDI-TOF-MS in a blinded analysis identified a combination of five biomarkers discriminating PD and healthy controls with 85% sensitivity and 70% specificity. 87 Finally, use of two-dimensional gel electrophoresis and mass spectrometry has so far yielded encouraging data supporting the possibility of developing a diagnostic biomarker on the basis of a proteomic fingerprint. 88,89 The potential for defining fingerprints of combinations of lipids is now being explored.…”

Biomarkers for trials of neuroprotection in Parkinson's disease

“…Advanced matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF) currently allows the identification of several proteins differing between PD and controls . A recent analysis of serum proteins captured by magnetic bead‐based weak cation exchange, followed by MALDI‐TOF MS, identified a combination of five biomarkers discriminating PD and healthy controls with 85.0% sensitivity and 70.0% specificity . Other approaches, including two‐dimensional gel electrophoresis and MS, show promise in being able to potentially reliably separate PD from controls and other disorders on the basis of a proteomic fingerprint.…”

“…Helpful in diagnosis of PD versus controls/other neurodegenerative diseases [147][148][149][150][151][152][153][154][155][156][157][158] Need further validation Potentially useful approach for novel biomarker development…”

“…152,153 A recent analysis of serum proteins captured by magnetic bead-based weak cation exchange, followed by MALDI-TOF MS, identified a combination of five biomarkers discriminating PD and healthy controls with 85.0% sensitivity and 70.0% specificity. 154 Other approaches, including twodimensional gel electrophoresis and MS, 155 show promise in being able to potentially reliably separate PD from controls and other disorders on the basis of a proteomic fingerprint. These new techniques using these specific proteins, however, need further validation in larger, independent samples to assess their suitability for eventual clinical application.…”

Evaluation of Protease Inhibitors Containing Tubes for MS-Based Plasma Peptide Profiling Studies

“…Advances in the field of proteomics have promoted a growing number of clinical studies with the exciting challenge of discovering new biomarkers for diagnosis and prognosis of human diseases . A magnetic bead based fractionation procedure coupled to matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry (MS) readout has been successfully used to profile the low molecular weight proteome of different body fluids in a rapid, reproducible, and highly automatable way . The fact that almost every cell of the organism sheds products into blood, leaving a record of its physiological state, makes blood an attractive source for biomarker discovery .…”