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 Coleman, Howard J. Federoff

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Fingerprint

Valproic Acid
Proteomics
Alzheimer Disease
Leukocytes
14-3-3 Proteins
Proteins
Neurodegenerative Diseases
Actins
rhoA GTP-Binding Protein
Annexin A1
Peroxiredoxins
Glyceraldehyde-3-Phosphate Dehydrogenases
Phosphoproteins
Mitogen-Activated Protein Kinase 1
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Leucine
Blood Cells
Mass Spectrometry
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

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

Cite this

Mhyre, T. R., Loy, R., Tariot, P. N., Profenno, L. A., Maguire-Zeiss, K. A., Zhang, D., ... Federoff, H. J. (2008). Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium. Neurobiology of Aging, 29(11), 1631-1643. https://doi.org/10.1016/j.neurobiolaging.2007.04.004

Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium. / Mhyre, Timothy R.; Loy, Rebekah; Tariot, Pierre N.; Profenno, Louis A.; Maguire-Zeiss, Kathleen A.; Zhang, Dabao; Coleman, Paul; Federoff, Howard J.

In: Neurobiology of Aging, Vol. 29, No. 11, 01.11.2008, p. 1631-1643.

Research output: Contribution to journalArticle

Mhyre, TR, Loy, R, Tariot, PN, Profenno, LA, Maguire-Zeiss, KA, Zhang, D, Coleman, P & Federoff, HJ 2008, 'Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium', Neurobiology of Aging, vol. 29, no. 11, pp. 1631-1643. https://doi.org/10.1016/j.neurobiolaging.2007.04.004
Mhyre, Timothy R. ; Loy, Rebekah ; Tariot, Pierre N. ; Profenno, Louis A. ; Maguire-Zeiss, Kathleen A. ; Zhang, Dabao ; Coleman, Paul ; Federoff, Howard J. / Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium. In: Neurobiology of Aging. 2008 ; Vol. 29, No. 11. pp. 1631-1643.
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