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

Fadi Abdi, Joseph F. Quinn, Joseph Jankovic, Martin McIntosh, James B. Leverenz, Elaine Peskind, Randy Nixon, John Nutt, Katherine Chung, Cyrus Zabetian, Ali Samii, Melanie Lin, Stephen Hattan, Catherine Pan, Yan Wang, Jinghua Jin, David Zhu, G. Jane Li, Yan Liu, Dana WaichunasThomas J. Montine, Jing Zhang

Research output: Contribution to journalArticle

306 Scopus citations

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
DOIs
StatePublished - 2006

Keywords

  • Alzheimer disease
  • Biomarkers
  • Parkinson disease
  • Proteomics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Abdi, F., Quinn, J. F., Jankovic, J., McIntosh, M., Leverenz, J. B., Peskind, E., Nixon, R., Nutt, J., Chung, K., Zabetian, C., Samii, A., Lin, M., Hattan, S., Pan, C., Wang, Y., Jin, J., Zhu, D., Li, G. J., Liu, Y., ... 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, 9(3), 293-348. https://doi.org/10.3233/JAD-2006-9309