Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer’s disease

  • M. S. Cheon
  • M. Fountoulakis
  • N. J. Cairns
  • M. Dierssen
  • K. Herkner
  • G. Lubec


Stathmin, distributed in neurons with high abundance, acts as an intracellular relay, integrating various transduction pathways triggered by extracellular signals and it is involved in physiological regulation of microtubule destabilization. Stathmin has been also shown to be a critical molecule in pathology of neurodegeneration such as Alzheimer’s disease (AD), particularly, in neurofibrillary tangle (NFT) formation. Here we evaluated protein levels of stathmin in adult brain from patients with AD and Down syndrome (DS) showing AD-like pathology by applying proteomic technologies with two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) identification and specific software for quantification of proteins. Significantly decreased protein levels of stathmin were observed in frontal (2.12 ± 1.17, n = 6) and temporal (3.05 ± 2.81, n = 10) cortices of AD compared to controls (frontal cortex: 4.41 ± 1.70, n = 8; temporal cortex: 5.26 ± 2.26, n = 13). Stathmin was also significantly decreased in frontal (2.47 ± 1.11, n = 7) and temporal (2.02 ± 1.18, n = 9) cortices of DS. We also investigated stathmin levels in fetal brain. Stathmin was not significantly changed between fetal DS brain and controls. We suggest that the decreased protein level of stathmin in brains is associated with tangle formation and microtubule instability in DS as well as AD, but stathmin is not involved in the abnormal development of fetal DS brain.


Down Syndrome Fetal Brain Neurobiol Aging Down Syndrome Patient Decrease Protein Level 
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  1. Amat JA, Fields KL, Schubart UK (1991) Distribution of phosphoprotein pl9 in rat brain during ontogeny: stage-specific expression in neurons and glia. Dev Brain Res 60: 205–218CrossRefGoogle Scholar
  2. Belmont LD, Mitchison TJ (1996) Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell 84: 623–631PubMedCrossRefGoogle Scholar
  3. Bendt P, Hobohm U, Langen H (1999) Reliable automatic protein identification from matrix-associated laser desorption/ionization mass spectrometric peptide fingerprints. Electrophoresis 20: 3521–3526CrossRefGoogle Scholar
  4. Bernert G, Nemethova M, Herrera-Marschitz M, Cairns N, Lubec G (1996) Decreased cyclin dependent kinase in brain of patients with Down syndrome. Neurosci Lett 216: 68–70PubMedCrossRefGoogle Scholar
  5. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254PubMedCrossRefGoogle Scholar
  6. Coleman PD, Kazee AM, Lapham L, Eskin T, Rogers K (1992) Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer’s disease. Neurobiol Aging 13: 631–639PubMedCrossRefGoogle Scholar
  7. Fountoulakis M, Langen H (1997) Identification of protein by matrix-assisted laser desorption ionization-mass spectroscopy following in-gel digestion in low-salt nonvolatile buffer and simplified peptide recovery. Anal Biochem 250: 153–156PubMedCrossRefGoogle Scholar
  8. Jin LW, Masliah E, Iimoto D, Deteresa R, Mallory M, Sundsmo M, Mori N, Sobel A, Saitoh T (1996) Neurofibrillary tangle-associated alteration of stathmin in Alzheimer’s disease. Neurobiol Aging 17: 331–341PubMedCrossRefGoogle Scholar
  9. Langen H, Roeder D, Juranville JF, Fountoulakis M (1997) Effect of the protein application mode and the acrylamide concentration on the resolution of protein spots separated by two-dimensional gel electrophoresis. Electrophoresis 18: 2085–2090PubMedCrossRefGoogle Scholar
  10. Langen H, Berndt P, Roder D, Cairns N, Lubec G, Fountoulakis M (1999) Two-dimensional map of human brain proteins. Electrophoresis 20: 907–916PubMedCrossRefGoogle Scholar
  11. Maucuer A, Moreau J, Mechali M, Sobel A (1993) The stathmin gene family: phylogenetic conservation and development regulation in Xenopus. J Biol Chem 268: 16420–16429PubMedGoogle Scholar
  12. Mirra SS, Heyman A, McKeel D, Sumi S, Crain BJ (1991) The consortium to establish a registry for Alzheimer’s disease. Neurology 41: 479–486PubMedCrossRefGoogle Scholar
  13. Nagy Z, Esiri MM, Smith AD (1998) The cell division cycle and the pathophysiology of Alzheimer’s disease. Neuroscience 87: 731–739PubMedCrossRefGoogle Scholar
  14. Okazaki T, Wang H, Masliah E, Cao M, Johnson SA, Sundsmao M, Saitoh T, Mori N (1995) SCG10, a neuronal-specific growth-associated protein in Alzheimer’s disease. Neurobiol Aging 16: 883–894PubMedCrossRefGoogle Scholar
  15. Peschanski M, Doye V, Hirsch E, Marty L, Dusart I, Manceau V, Sobel A (1993) Stathmin: cellular localization of a major phosphoprotein in the adult rat CNS, with a note on human forebrain. J Comp Neurol 337: 655–668PubMedCrossRefGoogle Scholar
  16. Saitoh T, Horsburgh K, Masliah E (1993) Hyperactivation of signal transduction system in Alzheimer’s disease. Ann NY Acad Sci 695: 34–41PubMedCrossRefGoogle Scholar
  17. Sobel A (1991) Stathmin: a relay phosphoprotein for multiple signal transduction? Trends Biochem Sci 16: 301–305PubMedCrossRefGoogle Scholar
  18. Tierney MC, Fisher RH, Lewis AJ, Torzitto ML, Snow WG, Reid DW, Nieuwstraaten P, Van Rooijen LAA, Derks HJGM, Van Wijk R, Bischop A (1988) The NINCDA ADRDA work group criteria for the clinical diagnosis of probable Alzheimer’s disease. Neurology 38: 359–364PubMedCrossRefGoogle Scholar
  19. Walczak CE (2000) Microtubule dynamics and tubulin interacting proteins. Curr Opin Cell Biol 12: 52–56PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • M. S. Cheon
    • 1
  • M. Fountoulakis
    • 2
  • N. J. Cairns
    • 3
  • M. Dierssen
    • 4
  • K. Herkner
    • 1
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaAustria
  2. 2.F. Hoffmann - La RocheBaselSwitzerland
  3. 3.Institute of Psychiatry, Brain BankKing’s CollegeUK
  4. 4.Medical and Molecular Genetics Center-IROHospital Duran i ReynalsBarcelonaSpain

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