Skip to main content
SpringerLink
Log in

Proteomic Profiling and Neurodegeneration in Alzheimer's Disease

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Quantitative proteome analysis of Alzheimer's disease (AD) brains was performed using 2-D gels to identify disease specific changes in protein expression. The task of characterizing the proteome and its components is now practically achievable because of the development and integration of four important tools: protein, EST, and complete genome sequence databases, mass spectrometry, matching software for protein sequences and protein separation technology. Mass spectrometry (MS) instrumentation has undergone a tremendous change over the past decade, culminating in the development of highly sensitive, robust instruments that can reliably analyze biomolecules, particularly proteins and peptides; we identified 35 proteins from over 100 protein spots on a 2-D gel. Using this current technology, protein-expression profiling, which is actually a specialized form of mining, is an important principal application of proteomics. The information obtained has tremendous potential as a means of determining the pathogenesis, and detecting disease markers and potential targets for drug therapy in AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mattson, M. P., Gary, D. S., Chan, S. L., and Duan, W. 2001. Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease. Biochem. Soc. Symp. 151-162.

  2. Paschen, W. and Frandsen, A. 2001. Endoplasmic reticulum dysfunction-a common denominator for cell injury in acute and degenerative diseases of the brain? J. Neurochem. 79:719-725.

    Google Scholar 

  3. Tsuji, T., Shimohama, S., Kimura, J., and Shimizu, K. 1998. m-Calpain (calcium-activated neutral proteinase) in Alzheimer's disease brains. Neurosci. Lett. 248:109-112.

    Google Scholar 

  4. Lopez, M. F., Kristal, B. S., Chernokalskaya, E., Lazarev, A., Shestopalov, A. I., Bogdanova, A., and Robinson, M. 2000. High-throughput profiling of the mitochondrial proteome using affinity fractionation and automation. Electrophoresis 21:3427-3440.

    Google Scholar 

  5. Maimone, D., Dominici, R., and Grimaldi, L. M. 2001. Pharmacogenomics of neurodegenerative diseases. Eur. J. Pharmacol. 413:11-29.

    Google Scholar 

  6. Taylor, J. E., Tinklenberg, J. R., Eng, L. F., Yesavage, J. A., Vinogradov, S., Davies, H. G., Gonzalez DeWhitt, P. A., and Frossard, P. M. 1988. Association study between Alzheimer's disease and restriction fragment length polymorphisms at the human amyloid beta protein gene locus. Mol. Biol. Med. 5:167-172.

    Google Scholar 

  7. Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F., and Whitehouse, C. M. 1989. Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64-71.

    Google Scholar 

  8. Mullan, M. 1992. Familial Alzheimer's disease: Second gene locus located [editorial]. BMJ 305:1108-1109.

    Google Scholar 

  9. Kidd, P. M. 2000. Attention deficit/hyperactivity disorder (ADHD) in children: rationale for its integrative management. Altern. Med. Rev. 5:402-428.

    Google Scholar 

  10. Blum, D., Torch, S., Lambeng, N., Nissou, M., Benabid, A. L., Sadoul, R., and Verna, J. M. 2001. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog. Neurobiol. 65:135-172.

    Google Scholar 

  11. Blennow, K., Vanmechelen, E., and Hampel, H. 2001. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Mol. Neurobiol. 24:87-97.

    Google Scholar 

  12. Tilleman, K., Stevens, I., Spittaels, K., Haute, C. V., Clerens, S., Van Den Bergh, G., Geerts, H., Van Leuven, F., Vandesande, F., and Moens, L. 2002. Differential expression of brain proteins in glycogen synthase kinase-3 transgenic mice: a proteomics point of view. Proteomics 2:94-104.

    Google Scholar 

  13. Wilkins, M. R., Sanchez, J. C., Gooley, A. A., Appel, R. D., Humphery-Smith, I., Hochstrasser, D. F., and Williams, K. L. 1996. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol. Genet. Eng. Rev. 13:19-50.

    Google Scholar 

  14. Shevchenko, A., Wilm, M., Vorm, O., and Mann, M. 1996. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68:850-858.

    Google Scholar 

  15. Mattila, K. M. and Frey, H. 1994. Alzheimer brain proteins investigated by two-dimensional gel electrophoresis with immobilized pH gradients in the first dimension [published erratum appears in Electrophoresis 1994 Jul; 15(7): following table of contents]. Electrophoresis 15:721-725.

    Google Scholar 

  16. Tsuji, T., Shimohama, S., Kamiya, S., Sazuka, T., and O'Hara, O. 1999. Analysis of brain proteins in Alzheimer's disease using high-resolution two-dimensional gel electrophoresis. J. Neurol. Sci. 166:100-106.

    Google Scholar 

  17. Edgar, P. F., Douglas, J. E., Knight, C., Cooper, G. J., Faull, R. L., and Kydd, R. 1999. Proteome map of the human hippocampus. Hippocampus 9:644-650.

    Google Scholar 

  18. Edgar, P. F., Schonberger, S. J., Dean, B., Faull, R. L., Kydd, R., and Cooper, G. J. 1999. A comparative proteome analysis of hippocampal tissue from schizophrenic and Alzheimer's disease individuals. Mol. Psychiatry 4:173-178.

    Google Scholar 

  19. Langen, H., Berndt, P., Roder, D., Cairns, N., Lubec, G., and Fountoulakis, M. 1999. Two-dimensional map of human brain proteins. Electrophoresis 20:907-916.

    Google Scholar 

  20. Schonberger, S. J., Edgar, P. F., Kydd, R., Faull, R. L., and Cooper, G. J. 2001. Proteomic analysis of the brain in Alzheimer's disease: Molecular phenotype of a complex disease process. Proteomics 1:1519-1528.

    Google Scholar 

  21. Gauss, C., Kalkum, M., Lowe, M., Lehrach, H., and Klose, J. 1999. Analysis of the mouse proteome. (I) Brain proteins: separation by two-dimensional electrophoresis and identification by mass spectrometry and genetic variation. Electrophoresis 20:575-600.

    Google Scholar 

  22. Rohlff, C. 2000. Proteomics in molecular medicine: applications in central nervous systems disorders. Electrophoresis 21:1227-1234.

    Google Scholar 

  23. Kilias, H., Gelfi, C., and Righetti, P. G. 1988. Isoenzyme analysis of lichen algae in immobilized pH gradients. Electrophoresis 9:187-191.

    Google Scholar 

  24. Adessi, C., Miege, C., Albrieux, C., and Rabilloud, T. 1997. Two-dimensional electrophoresis of membrane proteins: a current challenge for immobilized pH gradients. Electrophoresis 18:127-135.

    Google Scholar 

  25. Wilkins, M. R., Gasteiger, E., Sanchez, J. C., Bairoch, A., and Hochstrasser, D. F. 1998. Two-dimensional gel electrophoresis for proteome projects: the effects of protein hydrophobicity and copy number. Electrophoresis 19:1501-1505.

    Google Scholar 

  26. Anderson, N. L., Taylor, J., Scandora, A. E., Coulter, B. P., and Anderson, N. G. 1981. The TYCHO system for computer analysis of two-dimensional gel electrophoresis patterns. Clin. Chem. 27:1807-1820.

    Google Scholar 

  27. Rabilloud, T. 1996. Solubilization of proteins for electrophoretic analyses. Electrophoresis 17:813-829.

    Google Scholar 

  28. Henzel, W. J., Billeci, T. M., Stults, J. T., Wong, S. C., Grimley, C., and Watanabe, C. 1993. Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc. Natl. Acad. Sci. USA 90:5011-5015.

    Google Scholar 

  29. James, P., Quadroni, M., Carafoli, E., and Gonnet, G. 1993. Protein identification by mass profile fingerprinting. Biochem. Biophys. Res. Commun. 195:58-64.

    Google Scholar 

  30. Mann, M., Hojrup, P., and Roepstorff, P. 1993. Use of mass spectrometric molecular weight information to identify proteins in sequence databases. Biol. Mass Spectrom. 22:338-345.

    Google Scholar 

  31. Wilm, M., Shevchenko, A., Houthaeve, T., Breit, S., Schweigerer, L., Fotsis, T., and Mann, M. 1996. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature 379:466-469.

    Google Scholar 

  32. Shevchenko, A., Wilm, M., and Mann, M. 1997. Peptide sequencing by mass spectrometry for homology searches and cloning of genes. J. Protein Chem. 16:481-490.

    Google Scholar 

  33. Rabilloud, T., Adessi, C., Giraudel, A., and Lunardi, J. 1997. Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 18:307-316.

    Google Scholar 

  34. Roepstorff, P. 1997. Mass spectrometry in protein studies from genome to function. Curr. Opin. Biotechnol. 8:6-13.

    Google Scholar 

  35. Morris, H. R., Paxton, T., Dell, A., Langhorne, J., Berg, M., Bordoli, R. S., Hoyes, J., and Bateman, R. H. 1996. High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/orthogonal-acceleration time-of-flight mass spectrometer. Rapid Commun. Mass Spectrom. 10:889-896.

    Google Scholar 

  36. Morris, H. R., Paxton, T., Panico, M., McDowell, R., and Dell, A. 1997. A novel geometry mass spectrometer, the Q-TOF, for low-femtomole/attomole-range biopolymer sequencing. J. Prot. Chem. 16:469-479.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto, 606-8507, Japan

    T. Tsuji, A. Shiozaki, K. Yoshizato & S. Shimohama

  2. Developmental Biology Laboratory, Department of Biological Science, Faculty of Science, Hiroshima University, Higashihiroshima, 739-0046, Japan

    R. Kohno

Authors
  1. T. Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Shiozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Kohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Yoshizato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Shimohama
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsuji, T., Shiozaki, A., Kohno, R. et al. Proteomic Profiling and Neurodegeneration in Alzheimer's Disease. Neurochem Res 27, 1245–1253 (2002). https://doi.org/10.1023/A:1020941929414

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020941929414

Search

Navigation