Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid

Jing Zhang, David R. Goodlett, Elaine R. Peskind, Joseph Quinn, Yong Zhou, Qin Wang, Catherine Pan, Eugene Yi, Jimmy Eng, Ruedi H. Aebersold, Thomas J. Montine

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Identification of cerebrospinal fluid (CSF) biomarkers of the common age-related neurodegenerative diseases would be of great value to clinicians because of the difficulties in differential diagnoses of these diseases in clinical practice. Proteins are one class of potential biomarkers currently under investigation in the hope that different ensembles of proteins will aid in the diagnosis of these diseases, as well as in the assessment of progression and response to therapy. However, before undertaking a rational approach to CSF protein biomarkers of age-related neurodegeneration, we must first systematically identify CSF proteins and determine whether their levels change with normal aging. In this study, we used a powerful shotgun proteomic method, two-dimensional microcapillary liquid chromatography electrospray ionization tandem mass spectrometry, to identify proteins in human CSF. Additionally, using pooled CSF samples, we quantitatively compared the CSF proteome of younger adults with that of older adults using isotope-coded affinity tags (ICAT). From these studies we identified more than 300 proteins in CSF and found that there were 30 proteins with >20% change in concentrations between older and younger individuals. Finally, we validated changes in concentration for two of these proteins using Western blots in CSF from a separate set of individuals. These data not only expand substantially our current knowledge regarding human CSF proteins, but also supply the necessary information to appropriately interpret protein biomarkers of age-related neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)207-227
Number of pages21
JournalNeurobiology of Aging
Volume26
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Proteomics
Cerebrospinal Fluid Proteins
Cerebrospinal Fluid
Biomarkers
Proteins
Neurodegenerative Diseases
Electrospray Ionization Mass Spectrometry
Firearms
Proteome
Tandem Mass Spectrometry
Liquid Chromatography
Isotopes
Young Adult
Differential Diagnosis
Western Blotting

Keywords

  • Aging
  • Cerebrospinal fluid
  • ICAT
  • Proteins
  • Proteomics

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid. / Zhang, Jing; Goodlett, David R.; Peskind, Elaine R.; Quinn, Joseph; Zhou, Yong; Wang, Qin; Pan, Catherine; Yi, Eugene; Eng, Jimmy; Aebersold, Ruedi H.; Montine, Thomas J.

In: Neurobiology of Aging, Vol. 26, No. 2, 02.2005, p. 207-227.

Research output: Contribution to journalArticle

Zhang, J, Goodlett, DR, Peskind, ER, Quinn, J, Zhou, Y, Wang, Q, Pan, C, Yi, E, Eng, J, Aebersold, RH & Montine, TJ 2005, 'Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid', Neurobiology of Aging, vol. 26, no. 2, pp. 207-227. https://doi.org/10.1016/j.neurobiolaging.2004.03.012
Zhang, Jing ; Goodlett, David R. ; Peskind, Elaine R. ; Quinn, Joseph ; Zhou, Yong ; Wang, Qin ; Pan, Catherine ; Yi, Eugene ; Eng, Jimmy ; Aebersold, Ruedi H. ; Montine, Thomas J. / Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid. In: Neurobiology of Aging. 2005 ; Vol. 26, No. 2. pp. 207-227.
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