Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium

Timothy R. Mhyre, Rebekah Loy, Pierre N. Tariot, Louis A. Profenno, Kathleen A. Maguire-Zeiss, Dabao Zhang, Paul D. Coleman, Howard J. Federoff

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The molecular profiling of peripheral tissues, including circulating leukocytes, may hold promise in the discovery of biomarkers for diagnosing and treating neurodegenerative diseases, including Alzheimer's disease (AD). As a proof-of-concept, we performed a proteomics study on peripheral leukocytes from patients with AD both before and during treatment with divalproex sodium. Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, we identified 10 differentially expressed proteins: two up-regulated proteins, 14-3-3 protein ε and peroxiredoxin 2; and eight down-regulated proteins, actin-interacting protein, mitogen activated protein kinase 1, beta actin, annexin A1, glyceraldehyde 3-phosphate dehydrogenase, transforming protein RhoA, acidic leucine-rich nuclear phosphoprotein 32 family member B, and a currently unidentified protein. A subset was validated on both the transcript and protein levels in normal human peripheral blood mononuclear cell cultures treated with valproic acid. These proteins comprise a number of functional classes that may be important to the biology of AD and to the therapeutic action of valproate. These data also suggest the potential of using peripheral leukocytes to monitor pharmaceutical action for neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)1631-1643
Number of pages13
JournalNeurobiology of Aging
Issue number11
StatePublished - Nov 2008
Externally publishedYes


  • 2D electrophoresis
  • Alzheimer's disease
  • Biomarkers
  • GSK-3
  • Glycogen synthase kinase-3
  • HDAC
  • Histone deacetylase inhibitor
  • PBMC
  • Proteomics
  • VPA
  • Valproic acid
  • qRT-PCR

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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