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Gene Expression Studies on Human Trisomy 21 iPSCs and Neurons: Towards Mechanisms Underlying Down’s Syndrome and Early Alzheimer’s Disease-Like Pathologies

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Systems Biology of Alzheimer's Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1303))

Abstract

The cause of Alzheimer disease (AD) is not well understood and there is no cure. Our ability to understand the early events in the course of AD is severely limited by the difficulty of identifying individuals who are in the early, preclinical stage of this disease. Most individuals with Down’s syndrome (DS, trisomy 21) will predictably develop AD and that they will do so at a young age makes them an ideal population in which to study the early stages of AD. Several recent studies have exploited induced pluripotent stem cells (iPSCs) generated from individuals with familial AD, spontaneous AD and DS to attempt to identify early events and discover novel biomarkers of disease progression in AD. Here, we summarize the progress and limitations of these iPSC studies with a focus on iPSC-derived neurons. Further, we outline the methodology and results for comparing gene expression between AD and DS iPSC-derived neurons. We highlight differences and commonalities in these data that may implicate underlying genes and pathways that are causative for AD.

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References

  1. Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298:789–791

    CAS  PubMed  Google Scholar 

  2. Scheff SW, DeKosky ST, Price DA (1990) Quantitative assessment of cortical synaptic density in Alzheimer’s disease. Neurobiol Aging 11:29–37

    CAS  PubMed  Google Scholar 

  3. Scheff SW, Price DA (1998) Synaptic density in the inner molecular layer of the hippocampal dentate gyrus in Alzheimer disease. J Neuropathol Exp Neurol 57:1146–1153

    CAS  PubMed  Google Scholar 

  4. Scheff SW, Sparks DL, Price DA (1996) Quantitative assessment of synaptic density in the outer molecular layer of the hippocampal dentate gyrus in Alzheimer’s disease. Dementia 7:226–232

    CAS  PubMed  Google Scholar 

  5. Scheff SW, Sparks L, Price DA (1993) Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer’s disease. Ann Neurol 34:356–361

    CAS  PubMed  Google Scholar 

  6. Subbarao KV, Richardson JS, Ang LC (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J Neurochem 55:342–345

    CAS  PubMed  Google Scholar 

  7. Lovell MA, Ehmann WD, Butler SM, Markesbery WR (1995) Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 45:1594–1601

    CAS  PubMed  Google Scholar 

  8. Munch G, Thome J, Foley P et al (1997) Advanced glycation endproducts in ageing and Alzheimer’s disease. Brain Res Brain Res Rev 23:134–143

    CAS  PubMed  Google Scholar 

  9. Smith CD, Carney JM, Starke-Reed PE et al (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci U S A 88:10540–10543

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Mecocci P, MacGarvey U, Beal MF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 36:747–751

    CAS  PubMed  Google Scholar 

  11. Zana M, Janka Z, Kalman J (2007) Oxidative stress: a bridge between Down’s syndrome and Alzheimer’s disease. Neurobiol Aging 28:648–676

    CAS  PubMed  Google Scholar 

  12. Fillenbaum GG, van Belle G, Morris JC et al (2008) Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): the first twenty years. Alzheimers Dement 4:96–109

    PubMed Central  PubMed  Google Scholar 

  13. Mirra SS, Heyman A, McKeel D et al (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486

    CAS  PubMed  Google Scholar 

  14. Bertram L, Lill CM, Tanzi RE (2010) The genetics of Alzheimer disease: back to the future. Neuron 68:270–281

    CAS  PubMed  Google Scholar 

  15. Miyoshi K (2009) What is ‘early onset dementia’? Psychogeriatrics 9:67–72

    PubMed  Google Scholar 

  16. Presson AP, Partyka G, Jensen KM et al (2013) Current estimate of Down syndrome population prevalence in the United States. J Pediatr 163:1163–1168

    PubMed Central  PubMed  Google Scholar 

  17. Franceschi M, Comola M, Piattoni F et al (1990) Prevalence of dementia in adult patients with trisomy 21. Am J Med Genet 7(Suppl):306–308

    CAS  Google Scholar 

  18. Lai F, Williams RS (1989) A prospective study of Alzheimer disease in Down syndrome. Arch Neurol 46:849–853

    CAS  PubMed  Google Scholar 

  19. Lott IT, Head E, Doran E, Busciglio J (2006) Beta-amyloid, oxidative stress and Down syndrome. Curr Alzheimer Res 3:521–528

    CAS  PubMed  Google Scholar 

  20. McCarron M, Gill M, McCallion P, Begley C (2005) Health co-morbidities in ageing persons with Down syndrome and Alzheimer’s dementia. J Intellect Disabil Res 49:560–566

    CAS  PubMed  Google Scholar 

  21. Mori H (1997) The biological significance of neuropathological lesions in Alzheimer’s disease. Neurobiol Aging 18:379–382

    CAS  PubMed  Google Scholar 

  22. Schupf N, Patel B, Pang D et al (2007) Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol 64:1007–1013

    PubMed Central  PubMed  Google Scholar 

  23. Temple V, Jozsvai E, Konstantareas MM, Hewitt TA (2001) Alzheimer dementia in Down’s syndrome: the relevance of cognitive ability. J Intellect Disabil Res 45:47–55

    CAS  PubMed  Google Scholar 

  24. Urv TK, Zigman WB, Silverman W (2010) Psychiatric symptoms in adults with Down syndrome and Alzheimer’s disease. Am J Intellect Dev Disabil 115:265–276

    PubMed  Google Scholar 

  25. Zigman WB, Lott IT (2007) Alzheimer’s disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev 13:237–246

    PubMed  Google Scholar 

  26. Zigman WB, Schupf N, Sersen E, Silverman W (1996) Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard 100:403–412

    CAS  PubMed  Google Scholar 

  27. Moechars D, Dewachter I, Lorent K et al (1999) Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 274:6483–6492

    CAS  PubMed  Google Scholar 

  28. Wegiel J, Gong CX, Hwang YW (2011) The role of DYRK1A in neurodegenerative diseases. FEBS J 278:236–245

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Park IH, Arora N, Huo H et al (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  31. Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    CAS  PubMed  Google Scholar 

  32. Israel MA, Goldstein LS (2011) Capturing Alzheimer’s disease genomes with induced pluripotent stem cells: prospects and challenges. Genome Med 3:49

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Kondo T, Asai M, Tsukita K et al (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12:487–496

    CAS  PubMed  Google Scholar 

  34. Yagi T, Ito D, Okada Y et al (2011) Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20:4530–4539

    CAS  PubMed  Google Scholar 

  35. Yahata N, Asai M, Kitaoka S et al (2011) Anti-Abeta drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer’s disease. PLoS One 6:e25788

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Qiang L, Fujita R, Yamashita T et al (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146:359–371

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Martins-Taylor K, Nisler BS, Taapken SM et al (2011) Recurrent copy number variations in human induced pluripotent stem cells. Nat Biotechnol 29:488–491

    CAS  PubMed  Google Scholar 

  38. Gore A, Li Z, Fung HL et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63–67

    CAS  PubMed Central  PubMed  Google Scholar 

  39. McConnell MJ, Lindberg MR, Brennand KJ et al (2013) Mosaic copy number variation in human neurons. Science 342:632–637

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Chung CY, Khurana V, Auluck PK et al (2013) Identification and rescue of alpha-synuclein toxicity in Parkinson patient-derived neurons. Science 342:983–987

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Mali P, Yang L, Esvelt KM et al (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31:230–232

    CAS  PubMed  Google Scholar 

  43. Sanjana NE, Cong L, Zhou Y et al (2012) A transcription activator-like effector toolbox for genome engineering. Nat Protoc 7:171–192

    CAS  PubMed Central  PubMed  Google Scholar 

  44. McMahon MA, Rahdar M, Porteus M (2012) Gene editing: not just for translation anymore. Nat Methods 9:28–31

    CAS  Google Scholar 

  45. Jiang J, Jing Y, Cost GJ et al (2013) Translating dosage compensation to trisomy 21. Nature 500:296–300

    CAS  PubMed  Google Scholar 

  46. Fusaki N, Ban H, Nishiyama A et al (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Yu J, Hu K, Smuga-Otto K et al (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Papapetrou EP, Tomishima MJ, Chambers SM et al (2009) Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc Natl Acad Sci U S A 106:12759–12764

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Seki T, Yuasa S, Oda M et al (2010) Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7:11–14

    CAS  PubMed  Google Scholar 

  50. Meyer JS, Shearer RL, Capowski EE et al (2009) Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proc Natl Acad Sci U S A 106:16698–16703

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Oshima K, Shin K, Diensthuber M et al (2010) Mechanosensitive hair cell-like cells from embryonic and induced pluripotent stem cells. Cell 141:704–716

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Muguruma K, Nishiyama A, Ono Y et al (2010) Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nat Neurosci 13:1171–1180

    CAS  PubMed  Google Scholar 

  53. Zhang X, Huang CT, Chen J et al (2010) Pax6 is a human neuroectoderm cell fate determinant. Cell Stem Cell 7:90–100

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Pankratz MT, Li XJ, Lavaute TM et al (2007) Directed neural differentiation of hESCs via an obligated primitive anterior stage. Stem Cells 25:511–1520

    Google Scholar 

  55. Lavaute TM, Yoo YD, Pankratz MT et al (2009) Regulation of neural specification from human embryonic stem cells by BMP and FGF. Stem Cells 27:1741–1749

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Yoo YD, Huang CT, Zhang X et al (2011) Fibroblast growth factor regulates human neuroectoderm specification through ERK1/2-PARP-1 pathway. Stem Cells 29:1975–1982

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Chambers SM, Fasano CA, Papapetrou EP et al (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Johnson MA, Weick JP, Pearce RA, Zhang SC (2007) Functional neural development from human embryonic stem cells: accelerated synaptic activity via astrocyte coculture. J Neurosci 27:3069–3077

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Shi Y, Kirwan P, Livesey FJ (2012) Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks. Nat Protoc 7:1836–1846

    CAS  PubMed  Google Scholar 

  60. Siegenthaler JA, Pleasure SJ (2010) There’s no place like home for a neural stem cell. Cell Stem Cell 7:141–143

    CAS  PubMed  Google Scholar 

  61. Fasano CA, Chambers SM, Lee G et al (2010) Efficient derivation of functional floor plate tissue from human embryonic stem cells. Cell Stem Cell 6:336–347

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Liu H, Zhang SC (2011) Specification of neuronal and glial subtypes from human pluripotent stem cells. Cell Mol Life Sci 68:3995–4008

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Liu Y, Weick JP, Liu H et al (2013) Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits. Nat Biotechnol 31:440–447

    PubMed Central  PubMed  Google Scholar 

  64. Liu Y, Liu H, Sauvey C et al (2013) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc 8:1670–1679

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Wenk GL (2003) Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):7–10

    PubMed  Google Scholar 

  66. Cataldo AM, Peterhoff CM, Troncoso JC et al (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157:277–286

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Hooper C, Killick R, Lovestone S (2008) The GSK3 hypothesis of Alzheimer’s disease. J Neurochem 104:1433–1439

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Buytaert-Hoefen KA, Alvarez E, Freed CR (2004) Generation of tyrosine hydroxylase positive neurons from human embryonic stem cells after coculture with cellular substrates and exposure to GDNF. Stem Cells 22:669–674

    CAS  PubMed  Google Scholar 

  69. Zeng X, Cai J, Chen J et al (2004) Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22:925–940

    CAS  PubMed  Google Scholar 

  70. Bellefroid EJ, Kobbe A, Gruss P et al (1998) Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification. EMBO J 17:191–203

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Morizane A, Doi D, Kikuchi T et al (2011) Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells. J Neurosci Res 89:117–126

    CAS  PubMed  Google Scholar 

  72. Nishitsuji K, Tomiyama T, Ishibashi K et al (2009) The E693Delta mutation in amyloid precursor protein increases intracellular accumulation of amyloid beta oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells. Am J Pathol 174:957–969

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Briggs JA, Sun J, Shepherd J et al (2013) Integration-free induced pluripotent stem cells model genetic and neural developmental features of Down syndrome etiology. Stem Cells 31:467–478

    CAS  PubMed  Google Scholar 

  74. Shi Y, Kirwan P, Smith J et al (2012) A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Sci Transl Med 4:124ra29

    PubMed Central  PubMed  Google Scholar 

  75. Weick JP, Held DL, Bonadurer GF 3rd et al (2013) Deficits in human trisomy 21 iPSCs and neurons. Proc Natl Acad Sci U S A 110:9962–9967

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Becker LE, Mito T, Takashima S, Onodera K (1991) Growth and development of the brain in Down syndrome. Prog Clin Biol Res 373:133–152

    CAS  PubMed  Google Scholar 

  77. Bhattacharyya A, McMillan E, Chen SI et al (2009) A critical period in cortical interneuron neurogenesis in Down syndrome revealed by human neural progenitor cells. Dev Neurosci 31:497–510

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Esposito G, Imitola J, Lu J et al (2008) Genomic and functional profiling of human Down syndrome neural progenitors implicates S100B and Aquaporin 4 in cell injury. Hum Mol Genet 17:440–457

    CAS  PubMed  Google Scholar 

  79. Golden JA, Hyman BT (1994) Development of the superior temporal neocortex is anomalous in trisomy 21. J Neuropathol Exp Neurol 53:513–520

    CAS  PubMed  Google Scholar 

  80. Guidi S, Bonasoni P, Ceccarelli C et al (2008) Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome. Brain Pathol 18:180–197

    PubMed  Google Scholar 

  81. Guidi S, Ciani E, Bonasoni P et al (2011) Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with Down syndrome. Brain Pathol 21:361–373

    PubMed  Google Scholar 

  82. Ross MH, Galaburda AM, Kemper TL (1984) Down’s syndrome: is there a decreased population of neurons? Neurology 34:909–916

    CAS  PubMed  Google Scholar 

  83. Weitzdoerfer R, Dierssen M, Fountoulakis M, Lubec G (2001) Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. J Neural Transm Suppl (60): 59–70

    Google Scholar 

  84. Wisniewski KE, Laure-Kamionowska M, Wisniewski HM (1984) Evidence of arrest of neurogenesis and synaptogenesis in brains of patients with Down’s syndrome. N Engl J Med 311:1187–1188

    CAS  PubMed  Google Scholar 

  85. Busciglio J, Yankner BA (1995) Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 378:776–779

    CAS  PubMed  Google Scholar 

  86. Becker LE (1991) Synaptic dysgenesis. Can J Neurol Sci 18:170–180

    CAS  PubMed  Google Scholar 

  87. Takashima S, Becker LE, Armstrong DL, Chan F (1981) Abnormal neuronal development in the visual cortex of the human fetus and infant with Down’s syndrome. A quantitative and qualitative Golgi study. Brain Res 225:1–21

    CAS  PubMed  Google Scholar 

  88. Belichenko PV, Kleschevnikov AM, Salehi A et al (2007) Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. J Comp Neurol 504:329–345

    CAS  PubMed  Google Scholar 

  89. Chakrabarti L, Galdzicki Z, Haydar TF (2007) Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. J Neurosci 27:11483–11495

    CAS  PubMed  Google Scholar 

  90. Mao R, Zielke CL, Ronald ZH, Pevsner J (2003) Global up-regulation of chromosome 21 gene expression in the developing Down syndrome brain. Genomics 81:457–467

    CAS  PubMed  Google Scholar 

  91. Bahn S, Mimmack M, Ryan M et al (2002) Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down’s syndrome: a gene expression study. Lancet 359:310–315

    CAS  PubMed  Google Scholar 

  92. Cairney CJ, Sanguinetti G, Ranghini E et al (2009) A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging. Biochim Biophys Acta 1792:353–363

    CAS  PubMed  Google Scholar 

  93. Antonarakis SE, Lyle R, Chrast R, Scott HS (2001) Differential gene expression studies to explore the molecular pathophysiology of Down syndrome. Brain Res Brain Res Rev 36:265–274

    CAS  PubMed  Google Scholar 

  94. Lockstone HE, Harris LW, Swatton JE et al (2007) Gene expression profiling in the adult Down syndrome brain. Genomics 90:647–660

    CAS  PubMed  Google Scholar 

  95. Swatton JE, Sellers LA, Faull RL et al (2004) Increased MAP kinase activity in Alzheimer’s and Down syndrome but not in schizophrenia human brain. Eur J Neurosci 19:2711–2719

    PubMed  Google Scholar 

  96. Pradervand S, Paillusson A, Thomas J et al (2008) Affymetrix whole-transcript human gene 1.0 ST array is highly concordant with standard 3′ expression arrays. Biotechniques 44:759–762

    CAS  PubMed  Google Scholar 

  97. Irizarry RA, Hobbs B, Collin F et al (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    PubMed  Google Scholar 

  98. Carvalho BS, Irizarry RA (2010) A framework for oligonucleotide microarray preprocessing. Bioinformatics 26:2363–2367

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Keating DJ, Chen C, Pritchard MA (2006) Alzheimer’s disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1. Ageing Res Rev 5:388–401

    CAS  PubMed  Google Scholar 

  100. Mufson EJ, Conner JM, Kordower JH (1995) Nerve growth factor in Alzheimer’s disease: defective retrograde transport to nucleus basalis. Neuroreport 6:1063–1066

    CAS  PubMed  Google Scholar 

  101. Salehi A, Delcroix JD, Belichenko PV et al (2006) Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51:29–42

    CAS  PubMed  Google Scholar 

  102. Counts SE, Mufson EJ (2005) The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease. J Neuropathol Exp Neurol 64:263–272

    CAS  PubMed  Google Scholar 

  103. Cooper JD, Salehi A, Delcroix JD et al (2001) Failed retrograde transport of NGF in a mouse model of Down’s syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci U S A 98:10439–10444

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Wong SH, Xu Y, Zhang T, Hong W (1998) Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment. J Biol Chem 273:375–380

    CAS  PubMed  Google Scholar 

  105. Mullock BM, Smith CW, Ihrke G et al (2000) Syntaxin 7 is localized to late endosome compartments, associates with Vamp 8, and is required for late endosome-lysosome fusion. Mol Biol Cell 11:3137–3153

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Chen YA, Scheller RH (2001) SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol 2:98–106

    CAS  PubMed  Google Scholar 

  107. Wang W, Bouhours M, Gracheva EO et al (2008) ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1. Traffic 9:742–754

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Sakaba T, Kononenko NL, Bacetic J et al (2013) Fast neurotransmitter release regulated by the endocytic scaffold intersectin. Proc Natl Acad Sci U S A 110:8266–8271

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Pechstein A, Shupliakov O, Haucke V (2010) Intersectin 1: a versatile actor in the synaptic vesicle cycle. Biochem Soc Trans 38:181–186

    CAS  PubMed  Google Scholar 

  110. Cruts M, van Duijn CM, Backhovens H 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

    CAS  PubMed  Google Scholar 

  111. Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766

    CAS  PubMed  Google Scholar 

  112. Yoo S, Yoo C (2011) A statistical model that calculates the life time risk of Alzheimer’s disease using Bayesian Networks. Proceedings of 19th International Congress on Modeling and Simulation, Perth, Australia, 1049–1055, 2011 (http://www.mssanz.org.au/modsim2011/B4/yoo2.pdf)

  113. Boutillier S, Lannes B, Buee L et al (2007) Sp3 and sp4 transcription factor levels are increased in brains of patients with Alzheimer’s disease. Neurodegener Dis 4:413–423

    CAS  PubMed  Google Scholar 

  114. Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46

    CAS  PubMed  Google Scholar 

  115. Bush AI, Tanzi RE (2008) Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics 5:421–432

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Ferrer I, Barrachina M, Puig B et al (2005) Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 20:392–400

    CAS  PubMed  Google Scholar 

  117. Becker-Barroso E (2013) Strengthening connections between Down syndrome and AD. Lancet Neurol 12:931

    Google Scholar 

  118. Israel MA, Yuan SH, Bardy C et al (2012)Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482(7384):216–20

    Google Scholar 

  119. Martoglio B, Golde TE (2003) Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs. Hum Mol Genet 12:R201–6

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA

    Jason P. Weick & Huining Kang

  2. Waisman Center, University of Wisconsin-Madison, 623, 1500 Highland Avenue, Madison, WI, 53705, USA

    George F. Bonadurer III & Anita Bhattacharyya Ph.D.

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  1. Jason P. Weick
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  2. Huining Kang
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  3. George F. Bonadurer III
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  4. Anita Bhattacharyya Ph.D.
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Correspondence to Anita Bhattacharyya Ph.D. .

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Editors and Affiliations

  1. Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom

    Juan I. Castrillo

  2. Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom

    Stephen G. Oliver

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Weick, J.P., Kang, H., Bonadurer, G.F., Bhattacharyya, A. (2016). Gene Expression Studies on Human Trisomy 21 iPSCs and Neurons: Towards Mechanisms Underlying Down’s Syndrome and Early Alzheimer’s Disease-Like Pathologies. In: Castrillo, J., Oliver, S. (eds) Systems Biology of Alzheimer's Disease. Methods in Molecular Biology, vol 1303. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2627-5_15

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  • DOI: https://doi.org/10.1007/978-1-4939-2627-5_15

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2626-8

  • Online ISBN: 978-1-4939-2627-5

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