Skip to main content
SpringerLink
Log in

Proteomics Analysis in Alzheimer's Disease: New Insights into Mechanisms of Neurodegeneration

  • Reference work entry
  • First Online:
Handbook of Neurochemistry and Molecular Neurobiology

  • 663 Accesses

Abstract:

Redox proteomics is that branch of proteomics in which oxidatively modified proteins are identified using protein separation combined with mass spectrometry and bioinformatics. Using redox proteomics, brain and plasma proteins in Alzheimer's disease (AD) and models thereof that are oxidatively modified have been identified. Most oxidatively modified proteins are dysfunctional, suggesting that in AD the function of oxidatively modified proteins is compromised. Several categories of proteins ranging from those involved in energy metabolism, excitotoxicity, proteasome function, lipid asymmetry and cholinergic function, neuritic function, prevention of neuronal entrance to the cell cycle, hyperphosphorylation of tau, and amyloid beta‐peptide production, synaptic function, and pH buffering and carbon dioxide transport are oxidatively dysfunctional in AD brain. Redox proteomics studies of various models of AD recapitulate many of these oxidatively modified proteins. This review outlines these studies and posits that oxidatively dysfunctional proteins are intimately involved in the pathogenesis of AD.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AD:

Alzheimer's disease

2D‐PAGE:

Two‐dimensional gel electrophoresis

3‐NT:

3‐Nitrotyrosine

Aβ(1‐42):

Amyloid beta‐peptide 1‐42

apoE:

apolipoprotein E

APP:

Amyloid precursor protein

CAII:

Carbonic anhydrase II

CK:

Creatine kinase

CNS:

Central nervous system

Cpn60:

Chaperonin 60

DRP‐2:

Dihydropyrimidinase‐related protein 2

ESI:

Electrospray ionization

GAPDH:

Glyceraldehyde‐3‐phosphate dehydrogenase

GS:

Glutamine synthetase

GSK3β:

Glycogen synthase kinase 3β

HCNP:

Hippocampal cholinergic neurostimulating peptide

HNE:

4‐Hydroxy‐2‐nonenal

ICAT:

Isotopically coded affinity tags

IEF:

Isoelectric focusing

MALDI:

Matrix‐assisted laser desorption ionization

MCI:

Mild cognitive impairment

MS:

Mass spectrometry

NFT:

Neurofibrillary tangles

PEBP:

Phosphatidylethanolamine binding protein

Pin1:

Peptidy prolyl csi‐trans isomerase

SELDI:

Surface‐enhanced laser desorption ionization

SNAP:

Gamma‐soluble NSF attachment protein

TPI:

Triosephosphate isomerase

UCH L‐1:

Ubiquitin carboxy‐terminal hydrolase L‐1

References

  • Aebersold R, Goodlett DR. 2001. Mass spectrometry in proteomics. Chem Rev 101: 269–295.

    Article  CAS  PubMed  Google Scholar 

  • Agarwal-Mawal A, Qureshi HY, Cafferty PW, Yuan Z, Han D, et al. 2003. 14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex. J Biol Chem 278: 12722–12728.

    Article  CAS  PubMed  Google Scholar 

  • Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. 2001. Protein oxidation in the brain in Alzheimer's disease. Neuroscience 103: 373–383.

    Article  CAS  PubMed  Google Scholar 

  • Aksenova M, Butterfield DA, Zhang SX, Underwood M, Geddes JW. 2002. Increased protein oxidation and decreased creatine kinase BB expression and activity after spinal cord contusion injury. J Neurotrauma 19: 491–502.

    Article  PubMed  Google Scholar 

  • Aksenova MV, Aksenov MY, Payne RM, Trojanowski JQ, Schmidt ML, et al. 1999. Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders. Dement Geriatr Cogn Disord 10: 158–165.

    Article  CAS  PubMed  Google Scholar 

  • Arendt T. 2003. Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: The ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer's disease or the yin and yang of neuroplasticity. Prog Neurobiol 71: 83–248.

    Article  PubMed  Google Scholar 

  • Arimura N, Inagaki N, Chihara K, Menager C, Nakamura N, et al. 2000. Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse. J Biol Chem 275: 23973–23980.

    Article  CAS  PubMed  Google Scholar 

  • Beckers CJ, Block MR, Glick BS, Rothman JE, Balch WE. 1989. Vesicular transport between the endoplasmic reticulum and the Golgi stack requires the NEM-sensitive fusion protein. Nature 339: 397–398.

    Article  CAS  PubMed  Google Scholar 

  • Berlett BS, Stadtman ER. 1997. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272: 20313–20316.

    Article  CAS  PubMed  Google Scholar 

  • Blacker D, Wilcox MA, Laird NM, Rodes L, Horvath SM, et al. 1998. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet 19: 357–360.

    Article  CAS  PubMed  Google Scholar 

  • Boyd-Kimball D, Sultana R, Mohmmad-Abdul H, Butterfield DA. 2004a. Rodent Abeta(1–42) exhibits oxidative stress properties similar to those of human Abeta(1–42): Implications for proposed mechanisms of toxicity. J Alzheimers Dis 6: 515–525.

    Article  CAS  PubMed  Google Scholar 

  • Boyd-Kimball D, Mohmmad Abdul H, Reed T, Sultana S, Butterfield DA. 2004b. Role of phenylalanine 20 in Alzheimer's amyloid β-peptide (1–42)-induced oxidative stress and neurotoxicity. Chem Res Toxicol 17: 1743–1749.

    Article  CAS  PubMed  Google Scholar 

  • Boyd-Kimball D, Castegna A, Sultana R, Poon HF, Petroze R, et al. 2005a. Proteomic identification of proteins oxidized by Aβ(1–42) in synaptosomes: Implications for Alzheimer's disease. Brain Res 1044: 206-215.

    Article  CAS  PubMed  Google Scholar 

  • Boyd-Kimball D, Poon HF, Lynn BC, Cai J, Pierce WM, et al. 2006. Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Aβ(1–42): Implications for Alzheimer's disease. Neurobiol Aging 27: 1239-1249.

    Article  CAS  PubMed  Google Scholar 

  • Boyd-Kimball D, Sultana R, Poon HF, Lynn BC, Casamenti F, et al. 2005c. Proteomic identification of proteins specifically oxidized by intracerebral injection of Aβ(1–42) into rat brain: Implications for Alzheimer's disease. Neuroscience 132: 313–324.

    Article  CAS  PubMed  Google Scholar 

  • Bozner P, Wilson GL, Druzhyna NM, Bryant-Thomas TK, Le Doux SP, et al. 2002. Deficiency of chaperonin 60 in Down's syndrome. J Alzheimers Dis 4: 479–486.

    Article  CAS  PubMed  Google Scholar 

  • Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE. 2005. Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications. Ann Neurol 57: 695–703.

    Article  CAS  PubMed  Google Scholar 

  • Burkhard PR, Sanchex JC, Landis T, Hochstrasser DF. 2001. CSF detection of the 14-3-3 protein in unselected patients with dementia. Neurology 56: 1528–1533.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA. 2002. Amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: Implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res 36: 1307–1313.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA. 2003. Amyloid beta-peptide [1–42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer's disease brain: Mechanisms and consequences. Curr Med Chem 10: 2651–2659.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA. 2004. Proteomics: A new approach to investigate oxidative stress in Alzheimer's disease brain. Brain Res 1000: 1–7.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Lauderback CM. 2002. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: Potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32: 1050–1060.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Stadtman ER. 1997. Protein oxidation processes in aging brain. Adv Cell Aging Gerontol 2: 161–191.

    Article  CAS  Google Scholar 

  • Butterfield DA, Boyd-Kimball D, Castegna A. 2003. Proteomics in Alzheimer's disease: Insights into potential mechanisms of neurodegeneration. J Neurochem 86: 1313–1327.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Castegna A, Drake J, Scapagnini G, Calabrese V. 2002a. Vitamin E and neurodegenerative disorders associated with oxidative stress. Nutr Neurosci 5: 229–239.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Castegna A, Lauderback CM, Drake J. 2002b. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol Aging 23: 655–664.

    Article  PubMed  Google Scholar 

  • Butterfield DA, Hensley K, Cole P, Subramaniam R, Aksenov M, et al. 1997a. Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: Relevance to Alzheimer's disease. J Neurochem 68: 2451–2457.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Howard BJ, Yatin S, Allen KL, Carney JM. 1997b. Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 94: 674–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Butterfield DA, Poon HF, St. Clair D, Kellor JN, Pieree WM, Klein JB, Markesbary WR. 2006a. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: Insights into the development of Alzheimer's disease. Neurobiol Dis 22: 223-232.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Reed T, Perluigi M, De Marco C, Coccia R, Cini C, Sultana R. 2006b. Elevated protien-bound levels of the lipid peroxidatin product, 4-hydroxy-2-nonenal, in brain form persons with mild cognitive impairment. Neurosci Lett 397: 170-173.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Gnjec A, Poon HF, Castegna A, Pierce WM, Klein JB, Martins RN. 2006c. Redox proteomics identification of oxidatively modified brain proteins in inherited Alzheimer's disease: An initial assessment. J Alz Dis 10: 391-397.

    CAS  Google Scholar 

  • Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, et al. 2002a. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: Creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med 33: 562–571.

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Aksenov M, Thongboonkerd V, Klein JB., Pierce WM, et al. 2002b. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem 82: 1524–1532.

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Lauderback CM, Mohmmad-Abdul H, Butterfield DA. 2004a. Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: Implications for Alzheimer's disease. Brain Res 1004: 193–197.

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, et al. 2003. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J Neurochem 85: 1394–1401.

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Thongboonkerd V, Klein J, Lynn BC, Wang YL, et al. 2004b. Proteomic analysis of brain proteins in the gracile axonal dystrophy (gad) mouse, a syndrome that emanates from dysfunctional ubiquitin carboxyl-terminal hydrolase L-1, reveals oxidation of key proteins. J Neurochem 88: 1540–1546.

    Article  CAS  PubMed  Google Scholar 

  • Cesar Mde C, Wilson JE. 2004. All three isoforms of the voltage-dependent anion channel (VDAC1, VDAC2, and VDAC3) are present in mitochondria from bovine, rabbit, and rat brain. Arch Biochem Biophys 422: 191–196.

    Article  PubMed  CAS  Google Scholar 

  • Choi J, Malakowsky CA, Talent JM, Conrad CC, Carrll CA, et al. 2003. Anti-apoptotic proteins are oxidized by Abeta25–35 in Alzheimer's fibroblasts. Biochim Biophys Acta 1637: 135–141.

    Article  CAS  PubMed  Google Scholar 

  • Choi J, Malakowsky CA, Talent JM, Conrad CC, Gracy RW. 2002. Identification of oxidized plasma proteins in Alzheimer's disease. Biochem Biophys Res Commun 293: 1566–1570.

    Article  CAS  PubMed  Google Scholar 

  • Coleman PD, Flood DG. 1987. Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiol Aging 8: 521–545.

    Article  CAS  PubMed  Google Scholar 

  • Coyle JT, Price DL, DeLong MR. 1983. Alzheimer's disease: A disorder of cortical cholinergic innervation. Science 219: 1184–1190.

    Article  CAS  PubMed  Google Scholar 

  • Cruts M, van Duijn CM, Backhovens H, Van den Broeck M, Wehnert A, et al. 1998. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet 7: 43–51.

    Article  CAS  PubMed  Google Scholar 

  • Crystal H, Dickson D, Fuld P, Masur D, Scott R, et al. 1988. Clinico-pathologic studies in dementia: Nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38: 1682–1687.

    Article  CAS  PubMed  Google Scholar 

  • Dahiyat M, Cumming A, Harrington C, Wischik C, Xuereb J, et al. 1999. Association between Alzheimer's disease and the NOS3 gene. Ann Neurol 46: 664–667.

    Article  CAS  PubMed  Google Scholar 

  • Daleke DL, Lyles JV. 2000. Identification and purification of aminophospholipid flippases. Biochim Biophys Acta 1486: 108–127.

    Article  CAS  PubMed  Google Scholar 

  • Davies P. 1999. Challenging the cholinergic hypothesis in Alzheimer disease. JAMA 281: 1433–1434.

    Article  CAS  PubMed  Google Scholar 

  • Dougherty MK, Morrison, DK. 2004. Unlocking the code of 14-3-3. J Cell Sci 117: 1875–1884.

    Article  CAS  PubMed  Google Scholar 

  • Drake J, Link CD, Butterfield DA. 2003. Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid beta-peptide (1–42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24: 415–420.

    Article  CAS  PubMed  Google Scholar 

  • Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, et al. 2003. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem 84: 1173–1183.

    Article  CAS  PubMed  Google Scholar 

  • Fernley RT. 1988. Non-cytoplasmic carbonic anhydrases. Trends Biochem Sci 13: 356–359.

    Article  CAS  PubMed  Google Scholar 

  • Fountoulakis M, Cairns N, Lubec G. 1999. Increased levels of 14-3-3 gamma and epsilon proteins in brain f patients with Alzheimer's disease and Down syndrome. J Neural Transm Suppl 57: 323–335.

    CAS  PubMed  Google Scholar 

  • Frolich L. 2002. The cholinergic pathology in Alzheimer's disease – discrepancies between clinical experience and pathophysiological findings. J Neural Transm 109: 1003–1013.

    Article  CAS  PubMed  Google Scholar 

  • Fukata Y, Itoh TJ, Kimura T, Menager C, Nishimura T, et al. 2002. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol 4: 583–591.

    Article  CAS  PubMed  Google Scholar 

  • Giovannini MG, Scali C, Prosperi C, Bellucci A, Vannucchi MG, et al. 2002. Beta-amyloid-induced inflammation and cholinergic hypofunction in the rat brain in vivo: Involvement of the p38MAPK pathway. Neurobiol Dis 11: 257–274.

    Article  CAS  PubMed  Google Scholar 

  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, et al. 1991. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704–706.

    Article  CAS  PubMed  Google Scholar 

  • Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O. 2006. Ubiquitin hydrolase UCH-L1 rescues β-amyloid-induced decreases in synaptic function and contextual memory. Cell 126: 775-788.

    Article  CAS  PubMed  Google Scholar 

  • Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM. 1995. Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376: 509–514.

    Article  CAS  PubMed  Google Scholar 

  • Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, et al. 1986. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 261: 6084–6089.

    Article  CAS  PubMed  Google Scholar 

  • Gu Y, Ihara Y. 2000. Evidence that collapsin response mediator protein-2 is involved in the dynamics of microtubules. J Biol Chem 275: 17917–17920.

    Article  CAS  PubMed  Google Scholar 

  • Gylys KH, Fein JA, Yang F, Wiley DJ, Miller CA, et al. 2004. Synaptic changes in Alzheimer's disease: Increased amyloid-β and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol 165: 1809–1817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halliwell B. 2002. Hypothesis: Proteasome dysfunction: A primary event in neurodegeneration that leads to nitrative and oxidative stress and subsequent cell death. Ann N Y Acad Sci 962: 182–194.

    Article  CAS  PubMed  Google Scholar 

  • Hamajima N, Matsuda K, Sakata S, Tamaki N, Sasaki M, et al. 1996. A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene 180: 157–163.

    Article  CAS  PubMed  Google Scholar 

  • Hamos JE, DeGennaro LJ, Drachman DA. 1989. Synaptic loss in Alzheimer's disease and other dementias. Neurology 39: 355–361.

    Article  CAS  PubMed  Google Scholar 

  • Harada J, Sugimoto M. 1999. Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842: 311–323.

    Article  CAS  PubMed  Google Scholar 

  • Hashiguchi M, Sobue K, Paudel HK. 2000. 14-3-3 zeta is an effector of tau protein phosphorylation. JBC 275: 25247–25254.

    Article  CAS  Google Scholar 

  • Hashimoto M, Bar-on P, Ho G, Takenouchi T, Rockenstein E, et al. 2004. Beta-synuclein regulates Akt activity in neuronal cells: A possible mechanism for neuroprotection in Parkinson's disease. J Biol Chem, Published online.

    Google Scholar 

  • He Z, Tessier-Lavigne M. 1997. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90: 739–751.

    Article  CAS  PubMed  Google Scholar 

  • Hensley K, Hall N, Subramaniam R, Cole P, Harris M, et al. 1995. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem 65: 2146–2156.

    Article  CAS  PubMed  Google Scholar 

  • Herbert B. 1999. Advances in protein solubilization for two-dimensional gel electrophoresis. Electrophoresis 20: 660–663.

    Article  CAS  PubMed  Google Scholar 

  • Holzer M, Gartner U, Stobe A, Hartig W, Gruschka H, et al. 2002. Inverse association of Pin1 and tau accumulation in Alzheimer's disease hippocampus. Acta Neuropathol 104: 471–481.

    Article  CAS  PubMed  Google Scholar 

  • Hoogland C, Sanchez JC, Tonella L, Binz PA, Bairoch A, et al. 2000. The 1999 SWISS-2DPAGE database update. Nucl Acids Res 28: 286–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoyer S. 2004. Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: Therapeutic implications. Adv Exp Med Biol 541: 135–152.

    Article  CAS  PubMed  Google Scholar 

  • Hyun DH, Lee MH, Halliwell B, Jenner P. 2002. Proteasomal dysfunction induced by 4-hydroxy-2,3-trans-nonenal, an end-product of lipid peroxidation: A mechanism contributing to neurodegeneration? J Neurochem 83: 360–370.

    Article  CAS  PubMed  Google Scholar 

  • Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, et al. 2000. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 5: 142–149.

    Article  CAS  PubMed  Google Scholar 

  • Kaji H, Tsuji T, Mawuenyega KG, Wakamiya A, Taoka M, et al. 2000. Profiling of Caenorhabditis elegans proteins using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis 21: 1755–1765.

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Hamajima N, Inagaki H, Okamura N, Koji T, et al. 1998. Post-meiotic expression of the mouse dihydropyrimidinase-related protein 3 (DRP-3) gene during spermiogenesis. Mol Reprod Dev 51: 105–111.

    Article  CAS  PubMed  Google Scholar 

  • Keller JN, Hanni KB, Markesbery WR. 2000. Impaired proteasome function in Alzheimer's disease. J Neurochem 75: 436–439.

    Article  CAS  PubMed  Google Scholar 

  • Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, et al. 2005. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64: 1152–1156.

    Article  CAS  PubMed  Google Scholar 

  • Kolodkin AL, Levengood DV, Rowe EG, Tai YT, Giger RJ, et al. 1997. Neuropilin is a semaphorin III receptor. Cell 90: 753–762.

    Article  CAS  PubMed  Google Scholar 

  • Korolainen MA, Goldsteins G, Alafuzoff I, Koistinaho J, Pirttila T. 2002. Proteomic analysis of protein oxidation in Alzheimer's disease brain. Electrophoresis 23: 3428–3433.

    Article  CAS  PubMed  Google Scholar 

  • Kumar VB, Vyas K, Franko M, Choudhary V, Buddhiraju C, et al. 2001. Molecular cloning, expression, and regulation of hippocampal amyloid precursor protein of senescence accelerated mouse (SAMP8). Biochem Cell Biol 79: 57–67.

    Article  CAS  PubMed  Google Scholar 

  • Kurt MA, Davies DC, Kidd M, Duff K, Howlett DR. 2003. Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes. Neurobiol Dis 14: 89–97.

    Article  CAS  PubMed  Google Scholar 

  • Lang-Rollin I, Rideout H, Stefanis L. 2003. Ubiquitinated inclusions and neuronal cell death. Histol Histopathol 18: 509–517.

    CAS  PubMed  Google Scholar 

  • Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, et al. 2001. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: The role of Abeta1-42. J Neurochem 78: 413–416.

    Article  CAS  PubMed  Google Scholar 

  • Layfield R, Fergusson J, Aitken A, Lowe J, Landon M, et al. 1996. Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins. Neurosci Lett 209: 57–60.

    Article  CAS  PubMed  Google Scholar 

  • Leto TL, Fortugno-Erikson D, Barton D, Yang-Feng TL, Francke U, et al. 1988. Comparison of nonerythroid alpha-spectrin genes reveals strict homology among diverse species. Mol Cell Biol 8: 1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levy-Lahad E, Lahad A, Wijsman EM, Bird TD, Schellenberg GD. 1995. Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease. Ann Neurol 38: 678–680.

    Article  CAS  PubMed  Google Scholar 

  • Li JY, Henning Jensen P, Dahlstrom A. 2002. Differential localization of a-, b-, and g-synucleins in the rat CNS. Neuroscience 113: 463–478.

    Article  CAS  Google Scholar 

  • Lovell MA, Xie C, Markesbery WR. 2001. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging 22: 187–194.

    Article  CAS  PubMed  Google Scholar 

  • Lu, PJ, Wulf G, Zhou XZ, Davies P, Lu KP. 1999. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399: 784–788.

    Article  CAS  PubMed  Google Scholar 

  • Lubec G, Nonaka M, Krapfenbauer K, Gratzer M, Cairns N, et al. 1999. Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level. J Neural Transm Suppl 57: 161–177.

    CAS  PubMed  Google Scholar 

  • Luo Y, Raible D, Raper JA. 1993. Collapsin: A protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75: 217–227.

    Article  CAS  PubMed  Google Scholar 

  • Manczak M, Park BS, Jung Y, Reddy PH. 2004. Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: Implications for early mitochondrial dysfunction and oxidative damage. Neuromol Med 5: 147–162.

    Article  CAS  Google Scholar 

  • Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP. 1997. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem 68: 255–264.

    Article  CAS  PubMed  Google Scholar 

  • Markesbery WR. 1997. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 23: 134–147.

    Article  CAS  PubMed  Google Scholar 

  • Markesbery WR, Lovell MA. 1998. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging 19: 33–36.

    Article  CAS  PubMed  Google Scholar 

  • Masliah E, Alford M, De Teresa R, Mallory M, Hansen L. 1995. Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease. Ann Neurol 40: 759–766.

    Article  Google Scholar 

  • Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, et al. 1994. Synaptic and neuritic alterations during the progression of Alzheimer's disease. Neurosci Lett 174: 67–72.

    Article  CAS  PubMed  Google Scholar 

  • Matsuyama S, Xu Q, Velours J, Reed JC. 1998. The mitochondrial F0F1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells. Mol Cell 1: 327–336.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Partin J, Begley JG. 1998. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Res 807: 167–176.

    Article  CAS  PubMed  Google Scholar 

  • Mazzola JL, Sirover MA. 2001. Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer's disease and in Huntington's disease fibroblasts. J Neurochem 76: 442–449.

    Article  CAS  PubMed  Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, et al. 1984. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34: 939–944.

    Article  CAS  PubMed  Google Scholar 

  • Meier-Ruge W, Iwangoff P, Reichlmeier K. 1984. Neurochemical enzyme changes in Alzheimer's and Pick's disease. Arch Gerontol Geriatr 3: 161–165.

    Article  CAS  PubMed  Google Scholar 

  • Mohmmad-Abdul H, Butterfield DA. 2005. Protection against amyloid beta-peptide (1–42)-induced loss of phospholipid asymmetry in synaptosomal membranes by tricyclodecan-9-xanthogenate (D609) and ferulic acid ethyl ester: Implications for Alzheimer's disease. Biochim Biophys Acta 1741: 140-148.

    Article  CAS  PubMed  Google Scholar 

  • Molloy MP. 2000. Two-dimensional electrophoresis of membrane proteins using immobilized pH gradients. Anal Biochem 280: 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP. 2006. The prolyl isomerase Pinl regulates amyloid precursor protein processing and amyloid beta production. Nature 440: 528-534.

    Article  CAS  PubMed  Google Scholar 

  • Planel E, Miyasaka T, Launey T, Chui DH, Tanemura K, et al. 2004. Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: Implications for Alzheimer's disease. J Neurosci 24: 2401–2411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poon HF, Castegna A, Farr SA, Thongboonkerd V, Lynn BC, et al. 2004. Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain. Neuroscience 126: 915–926.

    Article  CAS  PubMed  Google Scholar 

  • Poon HF, Farr S, Thongboonkerd V, Lynn BC, Banks WA, et al. 2005a. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: Implications for aging and age-related neurodegenerative disorders. Neurochem Int 46: 159–168.

    Article  CAS  PubMed  Google Scholar 

  • Poon HF, Farr SA, Banks WA, Pierce WM, Klein JB, et al. 2005b. Proteomic identification of less oxidized brain proteins in aged senescence-accelerated mice following administration of antisense oligonucleotide directed at the Aβ region of amyloid precursor protein. Mol Brain Res 138: 8-16.

    Article  CAS  PubMed  Google Scholar 

  • Rabilloud T. 2002. Two-dimensional gel electrophoresis in proteomics: Old, old fashioned, but it still climbs up the mountains. Proteomics 2: 3–10.

    Article  CAS  PubMed  Google Scholar 

  • Ramakrishnan P, Dickson DW, Davies P. 2003. Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies. Neurobiol Dis 14: 251–264.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg RN. 2000. The molecular and genetic basis of AD: The end of the beginning: The 2000 Wartenberg lecture. Neurology 54: 2045–2054.

    Article  CAS  PubMed  Google Scholar 

  • Santoni V, Molloy M, Rabilloud T. 2000. Membrane proteins and proteomics: Un amour impossible? Electrophoresis 21: 1054–1070.

    Article  CAS  PubMed  Google Scholar 

  • Scheff SW, Price DA. 2003. Synaptic pathology in Alzheimer's disease: A review of ultrastructural studies. Neurobiol Aging 24: 1029–1046.

    Article  CAS  PubMed  Google Scholar 

  • Schutkowski M, Bernhardt A, Zhou XZ, Shen M, Reimer U, et al. 1998. Role of phosphorylation in determining the backbone dynamics of the serine/threonine-proline motif and Pin1 substrate recognition. Biochemistry 37: 5566–5575.

    Article  CAS  PubMed  Google Scholar 

  • Selkoe DJ. 2001. Presenilin, Notch, and the genesis and treatment of Alzheimer's disease. Proc Natl Acad Sci USA 98: 11039–11041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, et al. 1995. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375: 754–760.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu S, Narita M, Tsujimoto Y. 1999. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399: 483–487.

    Article  CAS  PubMed  Google Scholar 

  • Shringarpure R, Grune T, Sitte N, Davies KJ. 2000. 4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: Possible importance in Alzheimer's disease. Cell Mol Life Sci 57: 1802–1809.

    Article  CAS  PubMed  Google Scholar 

  • Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, et al. 1998. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: The Rotterdam study. Arch Neurol 55: 964–968.

    Article  CAS  PubMed  Google Scholar 

  • Sly WS, Hu, PY. 1995. Human carbonic anhydrases and carbonic anhydrase deficiencies. Annu Rev Biochem 64: 375–401.

    Article  CAS  PubMed  Google Scholar 

  • Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G. 1997. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci 17: 2653–2657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MA, Richey PL, Taneda S, Kutty RK, Sayre LM, et al. 1994. Advanced Maillard reaction end products, free radicals, and protein oxidation in Alzheimer's disease. Ann N Y Acad Sci 738: 447–454.

    Article  CAS  PubMed  Google Scholar 

  • Smith MA, Sayre LM, Monnier VM, Perry, G. 1996. Oxidative posttranslational modifications in Alzheimer disease. A possible pathogenic role in the formation of senile plaques and neurofibrillary tangles. Mol Chem Neuropathol 28: 41–48.

    Article  CAS  PubMed  Google Scholar 

  • Smolka MB, Zhou H, Purkayastha S, Aebersold R. 2001. Optimization of the isotope-coded affinity tag-labeling procedure for quantitative proteome analysis. Anal Biochem 297: 25–31.

    Article  CAS  PubMed  Google Scholar 

  • Soreghan B, Thomas SN, Yang AJ. 2003. Aberrant sphingomyelin/ceramide metabolic-induced neuronal endosomal/lysosomal dysfunction: Potential pathological consequences in age-related neurodegeneration. Adv Drug Deliv Rev 55: 1515–1524.

    Article  CAS  PubMed  Google Scholar 

  • Stenbeck G. 1998. Soluble NSF-attachment proteins. Int J Biochem Cell Biol 30: 573–577.

    Article  CAS  PubMed  Google Scholar 

  • Stevens SM Jr, Kem WR, Prokai, L. 2002. Investigation of cytolysin variants by peptide mapping: Enhanced protein characterization using complementary ionization and mass spectrometric techniques. Rapid Commun Mass Spectrom 16: 2094–2101.

    Article  CAS  PubMed  Google Scholar 

  • Subramaniam R, Roediger F, Jordan B, Mattson MP, Keller JN, et al. 1997. The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins. J Neurochem 69: 1161–1169.

    Article  CAS  PubMed  Google Scholar 

  • Sultana R, Butterfield DA. 2004. Oxidatively modified GST and MRP1 in Alzheimer's disease brain: Implications for accumulation of reactive lipid peroxidation products. Neurochem Res 29: 2215–2220.

    Article  CAS  PubMed  Google Scholar 

  • Sultana R, Boyd-Kimball D, Poon HF, Cai J, Pierce WM, et al. 2006a. Oxidative modification and down-regulation of Pin1 Alzheimer's disease hippocampus: A redox proteomics analysis. Neurobiol Aging 27: 918-925.

    Article  CAS  PubMed  Google Scholar 

  • Sultana R, Boyd-Kimball D, Poon HF, Cai J, Pierce WM, et al. 2006b. Regional redox proteomics to identify oxidized proteins in Alzheimer's disease brain: A mechanistic approach to understand pathological and biochemical alterations in AD. Neurobiol Aging 27: 1564-1576.

    Article  CAS  PubMed  Google Scholar 

  • Sultana R, Poon HF, Cai J, Pierce WM, Merchant M, et al. 2006c. Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approach. Neurobiol Dis 22: 76-87.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi Y. 2003. The 14-3-3 proteins: Gene, gene expression, and function. Neurochem Res 28: 1265–1273.

    Article  CAS  PubMed  Google Scholar 

  • Tilleman K, Stevens I, Spittaels K, Haute CV, Clerens S, et al. 2002. Differential expression of brain proteins in glycogen synthase kinase-3 transgenic mice: A proteomics point of view. Proteomics 2: 94–104.

    Article  CAS  PubMed  Google Scholar 

  • Vanderklish PW, Bahr BA. 2000. The pathogenic activation of calpain: A marker and mediator of cellular toxicity and disease states. Int J Exp Pathol 81: 323–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagner Y, Sickmann A, Meyer HE, Daum G. 2003. Multidimensional nano-HPLC for analysis of protein complexes. J Am Soc Mass Spectrom 14: 1003–1011.

    Article  CAS  PubMed  Google Scholar 

  • Wang LH, Strittmatter SM. 1996. A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16: 6197–6207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitzdoerfer R, Fountoulakis M, Lubec G. 2001. Aberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain. J Neural Transm Suppl 61: 95–107.

    Google Scholar 

  • Whitehouse PJ, Price DL, Clark AW, Coyle JT, Delong MR. 1981. Alzheimer's disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10: 122–126.

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson KD, Tashayev VL, O'Connor LB, Larsen CN, Kasperek E, et al. 1995. Metabolism of the polyubiquitin degradation signal: Structure, mechanism, and role of isopeptidase T. Biochemistry 34: 14535–14546.

    Article  CAS  PubMed  Google Scholar 

  • Yatin SM, Varadarajan S, Link CD, Butterfield DA. 1999. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid beta-peptide (1–42). Neurobiol Aging 20: 325–330; discussion 339–342.

    Article  CAS  PubMed  Google Scholar 

  • Yatin SM, Varadarajan S, Butterfield DA. 2000. Vitamin E prevents Alzheimer's amyloid beta-peptide (1–42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis 2: 123–131.

    Article  CAS  PubMed  Google Scholar 

  • Yoo BC, Fountoulakis M, Cairns N, Lubec G. 2001a. Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down syndrome. Electrophoresis 22: 172–179.

    Article  CAS  PubMed  Google Scholar 

  • Yoo BC, Kim SH, Cairns N, Fountoulakis M, Lubec G. 2001b. Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease. Biochem Biophys Res Commun 280: 249–258.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida H, Watanabe A, Ihara Y. 1998. Collapsin response mediator protein-2 is associated with neurofibrillary tangles in Alzheimer's disease. J Biol Chem 273: 9761–9768.

    Article  CAS  PubMed  Google Scholar 

  • Zhou XZ, Kops O, Werner A, Lu PJ, Shen M, et al. 2000. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Mol Cell 6: 873–883.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported, in part, by NIH grants [AG-05119; AG-10836].

Authors
  1. D. A. Butterfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Sultana
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha (Director) (Director)

  2. Technion‐Rappaport Family Faculty of Medicine, Efron St., POBox 9697, 31096, Haifa, Israel

    Moussa B. H. Youdim (Professor of Pharmacology Professor of Life Sciences Director of Eve Topf and NPF Centers of Excellence for Neurodegenerative Diseases Research) (Professor of Pharmacology Professor of Life Sciences Director of Eve Topf and NPF Centers of Excellence for Neurodegenerative Diseases Research)

  3. Clinic and Policlinic of Psychiatry and Psychotherapy Dept. Clinical Neurochemistry, University of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany

    Peter Riederer

  4. Eve Topf Center for Neurodegenerative Diseases Research and Dept. of Pharmacology, Faculty of Medicine Technion, Efron St., P.O.B. 9697, 31096, Haifa, Israel

    Sylvia A. Mandel

  5. Department of Neurosciences, University of Padova Medical School, Via Giustiniani 5, 35128, Padova, Italy

    Leontino Battistin

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this entry

Cite this entry

Butterfield, D.A., Sultana, R. (2007). Proteomics Analysis in Alzheimer's Disease: New Insights into Mechanisms of Neurodegeneration. In: Lajtha, A., Youdim, M.B.H., Riederer, P., Mandel, S.A., Battistin, L. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30377-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation