Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.
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.
Abdi
Fadi
F
Applied Biosystems, Framingham, MA, USA.
Quinn
Joseph F
JF
Jankovic
Joseph
J
McIntosh
Martin
M
Leverenz
James B
JB
Peskind
Elaine
E
Nixon
Randy
R
Nutt
John
J
Chung
Katherine
K
Zabetian
Cyrus
C
Samii
Ali
A
Lin
Melanie
M
Hattan
Stephen
S
Pan
Catherine
C
Wang
Yan
Y
Jin
Jinghua
J
Zhu
David
D
Li
G Jane
GJ
Liu
Yan
Y
Waichunas
Dana
D
Montine
Thomas J
TJ
Zhang
Jing
J
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
D015415:Biomarkers; D009419:Nerve Tissue Proteins