Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders

Fadi Abdi, Joseph Quinn, Joseph Jankovic, Martin McIntosh, James B. Leverenz, Elaine Peskind, Randy Nixon, John Nutt, Kathryn (Kathy) Chung, Cyrus Zabetian, Ali Samii, Melanie Lin, Stephen Hattan, Catherine Pan, Yan Wang, Jinghua Jin, David Zhu, G. Jane Li, Yan Liu, Dana Waichunas & 2 others Thomas J. Montine, Jing Zhang

Research output: Contribution to journalArticle

291 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)293-348
Number of pages56
JournalJournal of Alzheimer's Disease
Volume9
Issue number3
StatePublished - 2006

Fingerprint

Lewy Body Disease
Neurodegenerative Diseases
Proteomics
Cerebrospinal Fluid
Alzheimer Disease
Parkinson Disease
Biomarkers
Proteins
Cerebrospinal Fluid Proteins
Lewy Bodies
Proteome
Tandem Mass Spectrometry
Disease Progression
Chromatography
Autopsy
Western Blotting
Population

Keywords

  • Alzheimer disease
  • Biomarkers
  • Parkinson disease
  • Proteomics

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. / Abdi, Fadi; Quinn, Joseph; Jankovic, Joseph; McIntosh, Martin; Leverenz, James B.; Peskind, Elaine; Nixon, Randy; Nutt, John; Chung, Kathryn (Kathy); Zabetian, Cyrus; Samii, Ali; Lin, Melanie; Hattan, Stephen; Pan, Catherine; Wang, Yan; Jin, Jinghua; Zhu, David; Li, G. Jane; Liu, Yan; Waichunas, Dana; Montine, Thomas J.; Zhang, Jing.

In: Journal of Alzheimer's Disease, Vol. 9, No. 3, 2006, p. 293-348.

Research output: Contribution to journalArticle

Abdi, F, Quinn, J, Jankovic, J, McIntosh, M, Leverenz, JB, Peskind, E, Nixon, R, Nutt, J, Chung, KK, Zabetian, C, Samii, A, Lin, M, Hattan, S, Pan, C, Wang, Y, Jin, J, Zhu, D, Li, GJ, Liu, Y, Waichunas, D, Montine, TJ & Zhang, J 2006, 'Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders', Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 293-348.
Abdi, Fadi ; Quinn, Joseph ; Jankovic, Joseph ; McIntosh, Martin ; Leverenz, James B. ; Peskind, Elaine ; Nixon, Randy ; Nutt, John ; Chung, Kathryn (Kathy) ; Zabetian, Cyrus ; Samii, Ali ; Lin, Melanie ; Hattan, Stephen ; Pan, Catherine ; Wang, Yan ; Jin, Jinghua ; Zhu, David ; Li, G. Jane ; Liu, Yan ; Waichunas, Dana ; Montine, Thomas J. ; Zhang, Jing. / Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. In: Journal of Alzheimer's Disease. 2006 ; Vol. 9, No. 3. pp. 293-348.
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AU - McIntosh, Martin

AU - Leverenz, James B.

AU - Peskind, Elaine

AU - Nixon, Randy

AU - Nutt, John

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AU - Hattan, Stephen

AU - Pan, Catherine

AU - Wang, Yan

AU - Jin, Jinghua

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AU - Li, G. Jane

AU - Liu, Yan

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