title: Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.
abstract: Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.
authors.affiliation: Applied Biosystems, Framingham, MA, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Abdi
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Martin
authors.initials: M
authors.lastname: McIntosh
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Elaine
authors.initials: E
authors.lastname: Peskind
authors.forename: Randy
authors.initials: R
authors.lastname: Nixon
authors.forename: John
authors.initials: J
authors.lastname: Nutt
authors.forename: Katherine
authors.initials: K
authors.lastname: Chung
authors.forename: Cyrus
authors.initials: C
authors.lastname: Zabetian
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.forename: Melanie
authors.initials: M
authors.lastname: Lin
authors.forename: Stephen
authors.initials: S
authors.lastname: Hattan
authors.forename: Catherine
authors.initials: C
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Jin
authors.forename: David
authors.initials: D
authors.lastname: Zhu
authors.forename: G Jane
authors.initials: GJ
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Dana
authors.initials: D
authors.lastname: Waichunas
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D013058:Mass Spectrometry; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D040901:Proteomics; D011786:Quality Control; D012372:ROC Curve; D013048:Specimen Handling; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins