Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease

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

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Biomarkers to assist in the diagnosis and medical management of Alzheimer disease (AD) are a pressing need. We have employed a proteomic approach, microcapillary liquid chromatography mass spectrometry of proteins labeled with isotope-coded affinity tags (ICAT), to quantify relative changes in the proteome of human cerebrospinal fluid (CSF) obtained from the lumbar cistern. Using CSF from well-characterized AD patients and age-matched controls at 2 different institutions, we quantified protein concentration ratios of 42% of the 390 CSF proteins that we have identified and found differences ≥ 20% in over half of them. We confirmed our findings by western blot and validated this approach by quantifying relative levels of amyloid precursor protein and cathepsin B in 17 AD patients and 16 control individuals. Quantitative proteomics of CSF from AD patients compared to age-matched controls, as well as from other neurodegenerative diseases, will allow us to generate a roster of proteins that may serve as specific biomarker panels for AD and other geriatric dementias.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalJournal of Alzheimer's Disease
Volume7
Issue number2
DOIs
StatePublished - 2005

Keywords

  • Alzheimer disease
  • Biomarkers
  • Cerebrospinal fluid
  • Proteomics

ASJC Scopus subject areas

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

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