Summary
Systems biology offers enormous potential to understand the complexity of human brain aging and neurodegenerative diseases. Proteomics has an important role in these investigations because of its unique strengths and because of the potential central pathogenic contribution of pathological protein to several of these diseases. Here we have reviewed the methods and presented some examples of liquid chromatography—electrospray ionization—tandem mass spectrometry— based proteomics, with and without quantification using isotope-coded affinity tags, in the investigation of aging and Alzheimer’s disease. As protocols and methods for improved quantitative high-throughput proteomics constantly improve, this approach will likely continue to provide deeper insight into human brain aging and neurodegenerative diseases.
Key Words: Proteomics, Alzheimer’s disease, cerebrospinal fluid (CSF), neurofibrillary tangles
References
- 1.Wilson K, Ryan M, Prime J, Pashby D, Orange P, O’Beirne G, Whateley J, Bahn S, Morris C. Functional genomics and proteomics: application in neurosciences. J Neurol Neurosurg Psychiatry. 2004;75:529–538. doi: 10.1136/jnnp.2003.026260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ginsberg SD, Che S, Counts SE, Mufson EJ. Single cell gene expression profiling in Alzheimer’s Disease. NeuroRx. 2006;3:302–317. doi: 10.1016/j.nurx.2006.05.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Miller PM, Federoff HJ. Microarrays in Parkinson’s Disease: a systematic approach. NeuroRx. 2006;3:318–325. doi: 10.1016/j.nurx.2006.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Butterfield DA, Abdul HM, Newman S, Reed T. Redox proteomics in some age-related neurodegenerative disorders or models thereof. NeuroRx. 2006;3:343–356. doi: 10.1016/j.nurx.2006.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Choe LH, Werner BG, Lee KH. Two-dimensional protein electrophoresis: from molecular pathway discovery to biomarker discovery in neurological disorders. NeuroRx. 2006;3:326–334. doi: 10.1016/j.nurx.2006.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lukiw WJ, Bazan NG. Cyclooxygenase 2 RNA message abundance, stability, and hypervariablity in sporadic Alzheimer’s neocortex. J Neurosci Res. 1997;50:937–945. doi: 10.1002/(SICI)1097-4547(19971215)50:6<937::AID-JNR4>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
- 7.Lahm HW, Langen H. Mass spectrometry: a tool for the identification of proteins separated by gels. Electrophoresis. 2000;21:2105–2114. doi: 10.1002/1522-2683(20000601)21:11<2105::AID-ELPS2105>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
- 8.Lopez MF, Pluskal MG. Protein micro- and macroarrays: digitizing the proteome. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;787:19–27. doi: 10.1016/S1570-0232(02)00336-7. [DOI] [PubMed] [Google Scholar]
- 9.Aebersold R, Goodlett D. Mass spectrometry in proteomics. Chem Rev. 2001;101:269–295. doi: 10.1021/cr990076h. [DOI] [PubMed] [Google Scholar]
- 10.Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R. Quantitative analysis of complex protein mixtures using isotopecoded affinity tags. Nat Biotechnol. 1999;17:994–999. doi: 10.1038/13690. [DOI] [PubMed] [Google Scholar]
- 11.Goodlett DR, Yi EC. Proteomics without polyacrylamide: qualitative and quantitative uses of tandem mass spectrometry in proteome analysis. Funct Integr Genomics. 2002;2:138–153. doi: 10.1007/s10142-001-0041-3. [DOI] [PubMed] [Google Scholar]
- 12.Foret F, Preisler J. Liquid phase interfacing and miniaturization in matrix-assisted laser desorption/ionization mass spectrometry. Proteomics. 2002;2:360–372. doi: 10.1002/1615-9861(200204)2:4<360::AID-PROT360>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
- 13.Morris HR, Paxton T, Dell A, Langhome J, Berg M, Bordoli RS, Hoyes J, Bateman RH. High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/ orthogonal-acceleration time-of-flight mass spectrometer. Rapid Commun Mass Spectrom. 1996;10:889–896. doi: 10.1002/(SICI)1097-0231(19960610)10:8<889::AID-RCM615>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
- 14.Wu SL, Jardine I, Hancock WS, Karger BL. A new and sensitive on-line liquid chromatography/mass spectrometric approach for top-down protein analysis: the comprehensive analysis of human growth hormone in anE. coli lysate using a hybrid linear ion trap/Fourier transform ion cyclotron resonance mass spectrometer. Rapid Commun Mass Spectrom. 2004;18:2201–2207. doi: 10.1002/rcm.1609. [DOI] [PubMed] [Google Scholar]
- 15.Li XJ, Zhang H, Ranish JA, Aebersold R. Automated statistical analysis of protein abundance ratios from data generated by stable-isotope dilution and tandem mass spectrometry. Anal Chem. 2003;75:6648–6657. doi: 10.1021/ac034633i. [DOI] [PubMed] [Google Scholar]
- 16.Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, et al. Multiplexed protein quantitation inSaccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics. 2004;3:1154–1169. doi: 10.1074/mcp.M400129-MCP200. [DOI] [PubMed] [Google Scholar]
- 17.Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297:353–356. doi: 10.1126/science.1072994. [DOI] [PubMed] [Google Scholar]
- 18.Levy-Lahad E, Tsuang D, Bird TD. Recent advances in the genetics of Alzheimer’s disease. J Geriatr Psychiatry Neurol. 1998;11:42–54. doi: 10.1177/089198879801100202. [DOI] [PubMed] [Google Scholar]
- 19.Trojanowski JQ, Lee VM. Phosphorylation of paired helical filament tau in Alzheimer’s disease neurofibrillary lesions: focusing on phosphatases. FASEB J. 1995;9:1570–1576. doi: 10.1096/fasebj.9.15.8529836. [DOI] [PubMed] [Google Scholar]
- 20.Spillantini MG, Bird TD, Ghetti B. Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol. 1998;8:387–402. doi: 10.1111/j.1750-3639.1998.tb00162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Namba Y, Tomonaga M, Kawasaki H, Otomo E, Ikeda K. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt—Jakob disease. Brain Res. 1991;541:163–166. doi: 10.1016/0006-8993(91)91092-F. [DOI] [PubMed] [Google Scholar]
- 22.Lowe JS, Leigh N. Disorders of movement and system degenerations. In: Graham DI, Lantos PL, editors. Greenfield’s neuropathology. New York: Arnold Publishing; 2002. pp. 325–430. [Google Scholar]
- 23.Liao L, Cheng D, Wang J, Duong DM, Losik TG, Gearing M, et al. Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem. 2004;279:37061–37068. doi: 10.1074/jbc.M403672200. [DOI] [PubMed] [Google Scholar]
- 24.Wang Q, Woltjer RL, Cimino PJ, Pan C, Montine KS, Zhang J, Montine TJ. Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. FASEB J. 2005;19:869–871. doi: 10.1096/fj.04-2370com. [DOI] [PubMed] [Google Scholar]
- 25.Sirover MA. New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochim Biophys Acta. 1999;1432:159–184. doi: 10.1016/S0167-4838(99)00119-3. [DOI] [PubMed] [Google Scholar]
- 26.Mazzola JL, Sirover MA. Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders? Neurotoxicology. 2002;23:603–609. doi: 10.1016/S0161-813X(02)00062-1. [DOI] [PubMed] [Google Scholar]
- 27.Mazzola JL, Sirover MA. Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer’s disease fibroblasts. J Neurosci Res. 2003;71:279–285. doi: 10.1002/jnr.10484. [DOI] [PubMed] [Google Scholar]
- 28.Li Y, Nowotny P, Holmans P, Smemo S, Kauwe JS, Hinrichs AL, et al. Association of late-onset Alzheimer’s disease with genetic variation in multiple members of the GAPD gene family. Proc Natl Acad Sci USA. 2004;101:15688–15693. doi: 10.1073/pnas.0403535101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Montine TJ, Shinobu L, Montine KS, Roberts LJ, Beal MF, Morrow JD. No difference in plasma or urine F2-isoprostanes among patients with Huntington’s disease or Alzheimer’s disease, and controls. Ann Neurol. 2000;48:950–950. doi: 10.1002/1531-8249(200012)48:6<950::AID-ANA23>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
- 30.Montine TJ, Quinn JF, Milatovic D, Silbert LC, Dang T, Sanchez S, et al. Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer’s disease. Ann Neurol. 2002;52:175–179. doi: 10.1002/ana.10272. [DOI] [PubMed] [Google Scholar]
- 31.Andreasen N, Sjogren M, Blennow K. CSF markers for Alzheimer’s disease: total tau, phospho-tau and Aβ42. World J Biol Psychiatry. 2003;4:147–155. doi: 10.1080/15622970310029912. [DOI] [PubMed] [Google Scholar]
- 32.Clark C, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, et al. Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Arch Neurol. 2003;60:1696–1702. doi: 10.1001/archneur.60.12.1696. [DOI] [PubMed] [Google Scholar]
- 33.Galasko D. Cerebrospinal fluid biomarkers in Alzheimer’s disease: a fractional improvement? Arch Neurol. 2003;60:1195–1196. doi: 10.1001/archneur.60.9.1195. [DOI] [PubMed] [Google Scholar]
- 34.Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ, Morrow JD. Lipid peroxidation in aging brain and Alzheimer’s disease. Free Radic Biol Med. 2002;33:620–626. doi: 10.1016/S0891-5849(02)00807-9. [DOI] [PubMed] [Google Scholar]
- 35.Roberts LJ, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem. 1998;273:13605–13612. doi: 10.1074/jbc.273.22.13605. [DOI] [PubMed] [Google Scholar]
- 36.Zhang J, Goodlett DR, Peskind ER, Quinn JF, Zhou Y, Wang Q, et al. Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid. Neurobiol Aging. 2005;26:207–227. doi: 10.1016/j.neurobiolaging.2004.03.012. [DOI] [PubMed] [Google Scholar]
