Unraveling the complexity of neurodegeneration in brains of subjects with Down syndrome: Insights from proteomics

Proteomics - Clinical Applications

Volumn 8, Issue 1-2, 2014, Pages 73-85

  Perluigi, Marzia ^a   Di Domenico, Fabio ^a   Buttterfield, D Allan ^b,c  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Brain; Down syndrome; Neurodegeneration; Oxidative stress; Proteasome

Indexed keywords

AGING; ALZHEIMER DISEASE; AMNION FLUID; COGNITION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN SYNDROME; HUMAN; INTELLECTUAL IMPAIRMENT; MEMORY DISORDER; NERVE DEGENERATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NONHUMAN; OXIDATION REDUCTION POTENTIAL; OXIDATIVE STRESS; PHENOTYPE; PLACENTA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN HOMEOSTASIS; PROTEOMICS; REVIEW; SENILE PLAQUE;

AGING; ALZHEIMER DISEASE; AMNIOTIC FLUID; ANIMALS; BIOLOGICAL MARKERS; BRAIN; DEMENTIA; DOWN SYNDROME; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MALE; NERVE DEGENERATION; NERVE TISSUE PROTEINS; NEURONS; OXIDATIVE STRESS; PLACENTA; PREGNANCY; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEOMICS;

EID: 84893509799     PISSN: 18628346     EISSN: 18628354     Source Type: Journal    
DOI: 10.1002/prca.201300066     Document Type: Review

References (129)

1. Korenberg, J. R., Kawashima, H., Pulst, S. M., Ikeuchi, T. et al., Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. Am. J. Hum. Genet. 1990, 47, 236-246.
2. Antonarakis, S. E., Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphisms. Down Syndrome Collaborative Group. N. Engl. J. Med. 1991, 324, 872-876.
3. Delabar, J. M., Theophile, D., Rahmani, Z., Chettouh, Z. et al., Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur. J. Hum. Genet. 1993, 1, 114-124.
4. Korenberg, J. R., Chen, X. N., Schipper, R., Sun, Z. et al., Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc. Natl. Acad. Sci. USA 1994, 91, 4997-5001.
5. Antonarakis, S. E., Lyle, R., Chrast, R., Scott, H. S., Differential gene expression studies to explore the molecular pathophysiology of Down syndrome. Brain Res Brain Res Rev 2001, 36, 265-274.
6. Antonarakis, S. E., Lyle, R., Dermitzakis, E. T., Reymond, A., Deutsch, S., Chromosome 21 and down syndrome: from genomics to pathophysiology. Nat. Rev. Genet. 2004, 5, 725-738.
7. Iannello, R. C., Crack, P. J., de Haan, J. B., Kola, I., Oxidative stress and neural dysfunction in Down syndrome. J. Neural Transm. Suppl. 1999, 57, 257-267.
8. Burger, P. C., Vogel, F. S., The development of the pathologic changes of Alzheimer's disease and senile dementia in patients with Down's syndrome. Am. J. Pathol. 1973, 73, 457-476.
9. Wisniewski, K. E., Dalton, A. J., McLachlan, C., Wen, G. Y., Wisniewski, H. M., Alzheimer's disease in Down's syndrome: clinicopathologic studies. Neurology 1985, 35, 957-961.
10. Galdzicki, Z., Siarey, R. J., Understanding mental retardation in Down's syndrome using trisomy 16 mouse models. Genes Brain Behav. 2003, 2, 167-178.
11. Bush, A., Beail, N., Risk factors for dementia in people with down syndrome: issues in assessment and diagnosis. Am. J. Ment. Retard. 2004, 109, 83-97.
12. Zana, M., Janka, Z., Kalman, J., Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease. Neurobiol. Aging 2007, 28, 648-676.
13. Capone, G. T., Down syndrome: advances in molecular biology and the neurosciences. J. Dev. Behav. Pediatr. 2001, 22, 40-59.
14. Krasuski, J. S., Alexander, G. E., Horwitz, B., Rapoport, S. I., Schapiro, M. B., Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease. Am. J. Psychiatry 2002, 159, 74-81.
15. Teller, J. K., Russo, C., DeBusk, L. M., Angelini, G. et al., Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome. Nat. Med. 1996, 2, 93-95.
16. Gyure, K. A., Durham, R., Stewart, W. F., Smialek, J. E., Troncoso, J. C., Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome. Arch. Pathol. Lab. Med. 2001, 125, 489-492.
17. Perluigi, M., Butterfield, D. A., Oxidative stress and Down syndrome: A route toward Alzheimer-like dementia. Curr. Gerontol. Geriatr. Res. 2012, 2012, 724904.
18. Cenini, G., Dowling, A. L., Beckett, T. L., Barone, E. et al., Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome. Biochim. Biophys. Acta 2012, 1822, 130-138.
19. Reynolds, G. P., Cutts, A. J., Free radical damage in Down's syndrome brain. Biochem. Soc. Trans. 1993, 21, 221S.
20. Brooksbank, B. W., Martinez, M., Balazs, R., Altered composition of polyunsaturated fatty acyl groups in phosphoglycerides of Down's syndrome fetal brain. J. Neurochem. 1985, 44, 869-874.
21. Benzi, G., Moretti, A., Are reactive oxygen species involved in Alzheimer's disease? Neurobiol. Aging 1995, 16, 661-674.
22. Uttara, B., Singh, A. V., Zamboni, P., Mahajan, R. T., Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol. 2009, 7, 65-74.
23. Busciglio, J., Yankner, B. A., Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. Nature 1995, 378, 776-779.
24. Lott, I. T., Head, E., Doran, E., Busciglio, J., Beta-amyloid, oxidative stress and down syndrome. Curr. Alzheimer Res. 2006, 3, 521-528.
25. Cenini, G., Sultana, R., Memo, M., Butterfield, D. A., Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease. J. Cell. Mol. Med. 2008, 12, 987-994.
26. Cenini, G., Sultana, R., Memo, M., Butterfield, D. A., Effects of oxidative and nitrosative stress in brain on p53 proapoptotic protein in amnestic mild cognitive impairment and Alzheimer disease. Free Radic Biol Med 2008, 45, 81-85.
27. Pastor, M. C., Sierra, C., Dolade, M., Navarro, E. et al., Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome patients. Clin Chem 1998, 44, 924-929.
28. Shin, J. H., London, J., Le Pecheur, M., Hoger, H. et al., Aberrant neuronal and mitochondrial proteins in hippocampus of transgenic mice overexpressing human Cu/Zn superoxide dismutase 1. Free Radic. Biol. Med. 2004, 37, 643-653.
29. Gulesserian, T., Engidawork, E., Fountoulakis, M., Lubec, G., Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. J. Neural Transm. Suppl. 2001, 71-84.
30. Pratico, D., Iuliano, L., Amerio, G., Tang, L. X. et al., Down's syndrome is associated with increased 8, 12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo. Ann. Neurol. 2000, 48, 795-798.
31. Butterfield, D. A., Drake, J., Pocernich, C., Castegna, A., Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. Trends Mol. Med. 2001, 7, 548-554.
32. Butterfield, D. A., Galvan, V., Lange, M. B., Tang, H. et al., In vivo oxidative stress in brain of Alzheimer disease transgenic mice: requirement for methionine 35 in amyloid beta-peptide of APP. Free Radic. Biol. Med. 2010, 48, 136-144.
33. Mehta, P. D., Capone, G., Jewell, A., Freedland, R. L., Increased amyloid beta protein levels in children and adolescents with Down syndrome. J. Neurol. Sci. 2007, 254, 22-27.
34. Schupf, N., Zigman, W. B., Tang, M. X., Pang, D. et al., Change in plasma as peptides and onset of dementia in adults with Down syndrome. Neurology 2010, 75, 1639-1644.
35. Anandatheerthavarada, H. K., Biswas, G., Robin, M. A., Avadhani, N. G., Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J. Cell Biol. 2003, 161, 41-54.
36. Simon, A. M., Schiapparelli, L., Salazar-Colocho, P., Cuadrado-Tejedor, M. et al., Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol. Dis. 2009, 33, 369-378.
37. Rothermundt, M., Peters, M., Prehn, J. H., Arolt, V., S100B in brain damage and neurodegeneration. Microsc. Res. Tech. 2003, 60, 614-632.
38. Griffin, W. S., Sheng, J. G., McKenzie, J. E., Royston, M. C. et al., Life-long overexpression of S100beta in Down's syndrome: implications for Alzheimer pathogenesis. Neurobiol. Aging 1998, 19, 401-405.
39. Royston, M. C., McKenzie, J. E., Gentleman, S. M., Sheng, J. G. et al., Overexpression of s100beta in Down's syndrome: correlation with patient age and with beta-amyloid deposition. Neuropathol. Appl. Neurobiol. 1999, 25, 387-393.
40. Van Eldik, L. J., Griffin, W. S., S100 beta expression in Alzheimer's disease: relation to neuropathology in brain regions. Biochim. Biophys. Acta 1994, 1223, 398-403.
41. Pena, L. A., Brecher, C. W., Marshak, D. R., beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6 glioma and primary astrocyte cultures. Brain Res. Mol. Brain. Res. 1995, 34, 118-126.
42. Sanij, E., Hatzistavrou, T., Hertzog, P., Kola, I., Wolvetang, E. J., ETS-2 is induced by oxidative stress and sensitizes cells to H(2)O(2)-induced apoptosis: implications for Down's syndrome. Biochem. Biophys. Res. Commun. 2001, 287, 1003-1008.
43. Wolvetang, E. J., Wilson, T. J., Sanij, E., Busciglio, J. et al., ETS2 overexpression in transgenic models and in Down syndrome predisposes to apoptosis via the p53 pathway. Hum. Mol. Genet. 2003, 12, 247-255.
44. Balcz, B., Kirchner, L., Cairns, N., Fountoulakis, M., Lubec, G., Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down syndrome and Alzheimer's disease. J. Neural. Transm. Suppl. 2001, 61, 193-201.
45. Reed, T., Perluigi, M., Sultana, R., Pierce, W. M. et al., Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease. Neurobiol. Dis. 2008, 30, 107-120.
46. Breusing, N., Grune, T., Regulation of proteasome-mediated protein degradation during oxidative stress and aging. Biol. Chem. 2008, 389, 203-209.
47. Rock, K. L., Gramm, C., Rothstein, L., Clark, K. et al., Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 1994, 78, 761-771.
48. Chondrogianni, N., Petropoulos, I., Grimm, S., Georgila, K. et al., Protein damage, repair and proteolysis. Mol. Aspects Med. 2012.
49. Demartino, G. N., Gillette, T. G., Proteasomes: machines for all reasons. Cell 2007, 129, 659-662.
50. Tomko, R. J., Jr., Hochstrasser, M., Order of the proteasomal ATPases and eukaryotic proteasome assembly. Cell Biochem. Biophys. 2011, 60, 13-20.
51. Finley, D., Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 2009, 78, 477-513.
52. Tanaka, K., Mizushima, T., Saeki, Y., The proteasome: molecular machinery and pathophysiological roles. Biol. Chem. 2012, 393, 217-234.
53. Rivett, A. J., Proteasomes: multicatalytic proteinase complexes. Biochem. J. 1993, 291(Pt 1), 1-10.
54. Grune, T., Oxidative stress, aging and the proteasomal system. Biogerontology 2000, 1, 31-40.
55. Rivett, A. J., The multicatalytic proteinase. Multiple proteolytic activities. J. Biol. Chem. 1989, 264, 12215-12219.
56. Varshavsky, A., The ubiquitin system. Trends Biochem. Sci. 1997, 22, 383-387.
57. Hochstrasser, M., Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 1996, 30, 405-439.
58. van Nocker, S., Sadis, S., Rubin, D. M., Glickman, M. et al., The multiubiquitin-chain-binding protein Mcb1 is a component of the 26S proteasome in Saccharomyces cerevisiae and plays a nonessential, substrate-specific role in protein turnover. Mol. Cell Biol. 1996, 16, 6020-6028.
59. Wilkinson, K. D., Tashayev, V. L., O'Connor, L. B., Larsen, C. N. et al., Metabolism of the polyubiquitin degradation signal: structure, mechanism, and role of isopeptidase T. Biochemistry 1995, 34, 14535-14546.
60. Pan, J. X., Short, S. R., Goff, S. A., Dice, J. F., Ubiquitin pools, ubiquitin mRNA levels, and ubiquitin-mediated proteolysis in aging human fibroblasts. Exp. Gerontol. 1993, 28, 39-49.
61. Cuervo, A. M., Dice, J. F., How do intracellular proteolytic systems change with age? Front Biosci. 1998, 3, d25-d43.
62. Meek, D. W., Anderson, C. W., Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb. Perspect. Biol. 2009, 1, a000950.
63. Grune, T., Reinheckel, T., Davies, K. J., Degradation of oxidized proteins in mammalian cells. FASEB J. 1997, 11, 526-534.
64. Grune, T., Jung, T., Merker, K., Davies, K. J., Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease. Int. J. Biochem. Cell Biol. 2004, 36, 2519-2530.
65. Chondrogianni, N., Gonos, E. S., Proteasome inhibition induces a senescence-like phenotype in primary human fibroblasts cultures. Biogerontology 2004, 5, 55-61.
66. Chondrogianni, N., Gonos, E. S., Proteasome dysfunction in mammalian aging: steps and factors involved. Exp. Gerontol. 2005, 40, 931-938.
67. Petropoulos, I., Friguet, B., Protein maintenance in aging and replicative senescence: a role for the peptide methionine sulfoxide reductases. Biochim. Biophys. Acta 2005, 1703, 261-266.
68. Shringarpure, R., Grune, T., Davies, K. J., Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells. Cell Mol. Life Sci. 2001, 58, 1442-1450.
69. Friguet, B., Szweda, L. I., Stadtman, E. R., Susceptibility of glucose-6-phosphate dehydrogenase modified by 4-hydroxy-2-nonenal and metal-catalyzed oxidation to proteolysis by the multicatalytic protease. Arch. Biochem. Biophys. 1994, 311, 168-173.
70. Keller, J. N., Hanni, K. B., Markesbery, W. R., Possible involvement of proteasome inhibition in aging: implications for oxidative stress. Mech. Ageing Dev. 2000, 113, 61-70.
71. Chondrogianni, N., Gonos, E. S., Proteasome activation as a novel antiaging strategy. IUBMB Life 2008, 60, 651-655.
72. Engidawork, E., Juranville, J. F., Fountoulakis, M., Dierssen, M., Lubec, G., Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome. J. Neural. Transm. Suppl. 2001, 61, 117-130.
73. Di Domenico, F., Coccia, R., Cocciolo, A., Murphy, M. P. et al., Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer's disease neuropathology: redox proteomics analysis of human brain. Biochim. Biophys. Acta 2013, 1832, 1249-1259.
74. Oppermann, M., Cols, N., Nyman, T., Helin, J. et al., Identification of foetal brain proteins by two-dimensional gel electrophoresis and mass spectrometry comparison of samples from individuals with or without chromosome 21 trisomy. Eur. J. Biochem. 2000, 267, 4713-4719.
75. Cheon, M. S., Fountoulakis, M., Dierssen, M., Ferreres, J. C., Lubec, G., Expression profiles of proteins in fetal brain with Down syndrome. J. Neural Transm. Suppl. 2001, 61, 311-319.
76. Bajo, M., Fruehauf, J., Kim, S. H., Fountoulakis, M., Lubec, G., Proteomic evaluation of intermediary metabolism enzyme proteins in fetal Down's syndrome cerebral cortex. Proteomics 2002, 2, 1539-1546.
77. Shin, J. H., Weitzdoerfer, R., Fountoulakis, M., Lubec, G., Expression of cystathionine beta-synthase, pyridoxal kinase, and ES1 protein homolog (mitochondrial precursor) in fetal Down syndrome brain. Neurochem. Int. 2004, 45, 73-79.
78. Shin, J. H., Krapfenbauer, K., Lubec, G., Mass-spectrometrical analysis of proteins encoded on chromosome 21 in human fetal brain. Amino Acids 2006, 31, 435-447.
79. Brannvall, K., Hjelm, H., Korhonen, L., Lahtinen, U. et al., Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes. Biochem. Biophys. Res. Commun. 2003, 308, 369-374.
80. Lemere, C. A., Munger, J. S., Shi, G. P., Natkin, L. et al., The lysosomal cysteine protease, cathepsin-S, is increased in Alzheimers-disease and Down-syndrome brain - an immu-nocytochemical study. Am. J. Pathol. 1995, 146, 848-860.
81. Sun, Y., Dierssen, M., Toran, N., Pollak, D. D. et al., A gel-based proteomic method reveals several protein pathway abnormalities in fetal Down syndrome brain. J. Proteomics 2011, 74, 547-557.
82. Perluigi, M., Butterfield, D. A., The identification of protein biomarkers for oxidative stress in Down syndrome. Expert Rev. Proteomics 2011, 8, 427-429.
83. Kadota, M., Nishigaki, R., Wang, C. C., Toda, T. et al., Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome. Neuroscience 2004, 129, 325-335.
84. Shinohara, T., Tomizuka, K., Miyabara, S., Takehara, S. et al., Mice containing a human chromosome 21 model behavioral impairment and cardiac anomalies of Down's syndrome. Hum. Mol. Genet. 2001, 10, 1163-1175.
85. Gulesserian, T., Seidl, R., Hardmeier, R., Cairns, N., Lubec, G., Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome. J. Investig. Med. 2001, 49, 41-46.
86. Yoo, B. C., Vlkolinsky, R., Engidawork, E., Cairns, N. et al., Differential expression of molecular chaperones in brain of patients with Down syndrome. Electrophoresis 2001, 22, 1233-1241.
87. Shin, J. H., Gulesserian, T., Verger, E., Delabar, J. M., Lubec, G., Protein dysregulation in mouse hippocampus polytransgenic for chromosome 21 structures in the Down syndrome critical region. J. Proteome Res. 2006, 5, 44-53.
88. Butterfield, D. A., Perluigi, M., Reed, T., Muharib, T. et al., Redox proteomics in selected neurodegenerative disorders: from its infancy to future applications. Antioxid. Redox Signal 2012, 17, 1610-1655.
89. Wang, Y., Mulligan, C., Denyer, G., Delom, F. et al., Quantitative proteomics characterization of a mouse embryonic stem cell model of Down syndrome. Mol. Cell. Proteomics 2009, 8, 585-595.
90. O'Doherty, A., Ruf, S., Mulligan, C., Hildreth, V. et al., An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 2005, 309, 2033-2037.
91. Seidl, R., Cairns, N., Lubec, G., The brain in Down syndrome. J. Neural Transm. Suppl. 2001, 61, 247-261.
92. Lubec, G., Engidawork, E., The brain in Down syndrome (TRISOMY 21). J. Neurol. 2002, 249, 1347-1356.
93. Sanchez, L., Alvarez, V., Gonzalez, P., Gonzalez, I. et al., Variation in the LRP-associated protein gene (LRPAP1) is associated with late-onset Alzheimer disease. Am. J. Med. Genet. 2001, 105, 76-78.
94. Mulder, S. D., Veerhuis, R., Blankenstein, M. A., Nielsen, H. M., The effect of amyloid associated proteins on the expression of genes involved in amyloid-beta clearance by adult human astrocytes. Exp. Neurol. 2012, 233, 373-379.
95. Fernandez, F., Trinidad, J. C., Blank, M., Feng, D. D. et al., Normal protein composition of synapses in Ts65Dn mice: a mouse model of Down syndrome. J. Neurochem. 2009, 110, 157-169.
96. Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A. et al., A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat. Genet. 1995, 11, 177-184.
97. Pollonini, G., Gao, V., Rabe, A., Palminiello, S. et al., Abnormal expression of synaptic proteins and neurotrophin-3 in the Down syndrome mouse model Ts65Dn. Neuroscience 2008, 156, 99-106.
98. Siddiqui, A., Lacroix, T., Stasko, M. R., Scott-McKean, J. J. et al., Molecular responses of the Ts65Dn and Ts1Cje mouse models of Down syndrome to MK-801. Genes Brain Behav. 2008, 7, 810-820.
99. Belichenko, P. V., Kleschevnikov, A. M., Masliah, E., Wu, C. et al., Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome. J. Comp. Neurol. 2009, 512, 453-466.
100. Ishihara, K., Amano, K., Takaki, E., Ebrahim, A. S. et al., Increased lipid peroxidation in Down's syndrome mouse models. J. Neurochem. 2009, 110, 1965-1976.
101. Amano, K., Sago, H., Uchikawa, C., Suzuki, T. et al., Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome. Hum. Mol. Genet. 2004, 13, 1333-1340.
102. Richtsmeier, J. T., Zumwalt, A., Carlson, E. J., Epstein, C. J., Reeves, R. H., Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome. Am. J. Med. Genet. 2002, 107, 317-324.
103. Sago, H., Carlson, E. J., Smith, D. J., Kilbridge, J. et al., Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc. Natl. Acad. Sci. USA 1998, 95, 6256-6261.
104. Sultana, R., Perluigi, M., Allan Butterfield, D., Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radic. Biol. Med. 2013, 62, 157-169.
105. Tsangaris, G. T., Karamessinis, P., Kolialexi, A., Garbis, S. D. et al., Proteomic analysis of amniotic fluid in pregnancies with Down syndrome. Proteomics 2006, 6, 4410-4419.
106. French, M. M., Smith, S. E., Akanbi, K., Sanford, T. et al., Expression of the heparan sulfate proteoglycan, perlecan, during mouse embryogenesis and perlecan chondrogenic activity in vitro. J. Cell. Biol. 1999, 145, 1103-1115.
107. Govindraj, P., West, L., Koob, T. J., Neame, P. et al., Isolation and identification of the major heparan sulfate proteoglycans in the developing bovine rib growth plate. J. Biol. Chem. 2002, 277, 19461-19469.
108. Anwar, A. J., Walker, J. D., Frier, B. M., Type 1 diabetes mellitus and Down's syndrome: prevalence, management and diabetic complications. Diabet. Med. 1998, 15, 160-163.
109. Rohrer, T. R., Hennes, P., Thon, A., Dost, A. et al., Down's syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes. Diabetologia 2010, 53, 1070-1075.
110. Bergholdt, R., Eising, S., Nerup, J., Pociot, F., Increased prevalence of Down's syndrome in individuals with type 1 diabetes in Denmark: a nationwide population-based study. Diabetologia 2006, 49, 1179-1182.
111. Park, J., Cha, D. H., Jung, J. W., Kim, Y. H. et al., Comparative proteomic analysis of human amniotic fluid supernatants with Down syndrome using mass spectrometry. J. Microbiol. Biotechnol. 2010, 20, 959-967.
112. Cho, C. K., Smith, C. R., Diamandis, E. P., Amniotic fluid proteome analysis from Down syndrome pregnancies for biomarker discovery. J. Proteome Res. 2010, 9, 3574-3582.
113. Cho, C. K., Drabovich, A. P., Batruch, I., Diamandis, E. P., Verification of a biomarker discovery approach for detection of Down syndrome in amniotic fluid via multiplex selected reaction monitoring (SRM) assay. J. Proteomics 2011, 74, 2052-2059.
114. Perluigi, M., di Domenico, F., Fiorini, A., Cocciolo, A. et al., Oxidative stress occurs early in Down syndrome pregnancy: a redox proteomics analysis of amniotic fluid. Proteomics Clin. Appl. 2011, 5, 167-178.
115. Helbecque, N., Codron, V., Cottel, D., Amouyel, P., An apolipoprotein A-I gene promoter polymorphism associated with cognitive decline, but not with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 2008, 25, 97-102.
116. Cho, C. K., Drabovich, A. P., Karagiannis, G. S., Martinez-Morillo, E. et al., Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in Down syndrome. Clin. Proteomics 2013, 10, 2.
117. Sun, C. J., Yan, L. Y., Wang, W., Yu, S. et al., Proteomic analysis of the alteration of protein expression in the placenta of Down syndrome. Chin. Med. J. (Engl.) 2011, 124, 3738-3745.
118. Cabras, T., Pisano, E., Montaldo, C., Giuca, M. R. et al., Significant modifications of the salivary proteome potentially associated with complications of Down syndrome revealed by top-down proteomics. Mol. Cell. Proteomics 2013, 12, 1844-1852.
119. Gustaw, K. A., Garrett, M. R., Lee, H. G., Castellani, R. J. et al., Antigen-antibody dissociation in Alzheimer disease: a novel approach to diagnosis. J. Neurochem. 2008, 106, 1350-1356.
120. Yan, S. D., Zhu, H., Zhu, A., Golabek, A. et al., Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis. Nat. Med. 2000, 6, 643-651.
121. Sasaki, N., Toki, S., Chowei, H., Saito, T. et al., Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease. Brain Res. 2001, 888, 256-262.
122. Kolla, V., Jeno, P., Moes, S., Tercanli, S. et al., Quantitative proteomics analysis of maternal plasma in Down syndrome pregnancies using isobaric tagging reagent (iTRAQ). J. Biomed. Biotechnol. 2010, 2010, 952047.
123. Heywood, W., Mills, K., Wang, D., Hogg, J. et al., Identification of new biomarkers for Down's syndrome in maternal plasma. J Proteomics 2012, 75, 2621-2628.
124. Yu, B., Zhang, B., Wang, J., Wang, Q. W. et al., Preliminary proteomic-based identification of a novel protein for Down's syndrome in maternal serum. Exp. Biol. Med. (Maywood) 2012, 237, 530-539.
125. Kang, Y., Dong, X., Zhou, Q., Zhang, Y. et al., Identification of novel candidate maternal serum protein markers for Down syndrome by integrated proteomic and bioinformatic analysis. Prenat. Diagn. 2012, 32, 284-292.
126. Heywood, W. E., Madgett, T. E., Wang, D., Wallington, A. et al., 2D DIGE analysis of maternal plasma for potential biomarkers of Down Syndrome. Proteome Sci. 2011, 9, 56.
127. Mastricci, A. L., Akolekar, R., Kuppusamy, R., Ahmed, M., Nicolaides, K. H., Are serum protein biomarkers derived from proteomic analysis useful in screening for trisomy 21 at 11-13 weeks? Fetal Diagn. Ther. 2011, 30, 53-59.
128. Kolialexi, A., Tsangaris, G. T., Papantoniou, N., Anagnostopoulos, A. K. et al., Application of proteomics for the identification of differentially expressed protein markers for Down syndrome in maternal plasma. Prenat Diagn. 2008, 28, 691-698.
129. Nagalla, S. R., Canick, J. A., Jacob, T., Schneider, K. A. et al., Proteomic analysis of maternal serum in down syndrome: identification of novel protein biomarkers. J. Proteome. Res. 2007, 6, 1245-1257.