Skip to main content
SpringerLink
Log in

Gene Delivery and Gene Therapy for Alzheimer’s Disease

  • Protocol
  • First Online:
Gene Delivery and Therapy for Neurological Disorders

Part of the book series: Neuromethods ((NM,volume 98))

Abstract

Adeno-associated virus (AAV) is the most widely used vector for gene therapy clinical trials focused on neurodegeneration. Not only can it safely and efficiently confer long-term expression in a variety of cell types, but innovations including hybrid serotypes, rationally designed capsids, split vectors, specific promoter/enhancer additions, and convection-enhanced delivery have greatly progressed the field of AAV research for neurodegenerative disease. Indeed, these developments, which enable increased specificity, efficiency, and spread of gene transfer as well as ease of administration to the CNS, have pushed AAV forward into clinical trials for Alzheimer’s disease. Preclinical testing of AAV gene transfer efficacy in animal models of disease has thus intensified. In this chapter, we provide detailed methods for construction of AAV expression vectors, their application in preclinical studies using established animal models of Alzheimer’s disease, and evaluation methods to assess Alzheimer’s disease-like behavior and brain pathology.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

References

  1. Lim ST, Airavaara M, Harvey BK (2010) Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS. Pharmacol Res 61:14–26

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Atchison RW, Casto BC, Hammon WM (1965) Adenovirus-associated defective virus particles. Science 149:754–756

    CAS  PubMed  Google Scholar 

  3. Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci U S A 55:1467–1474

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Casto BC, Atchison RW, Hammon WM (1967) Studies on the relationship between adeno-associated virus type I (AAV-1) and adenoviruses. I. Replication of AAV-1 in certain cell cultures and its effect on helper adenovirus. Virology 32:52–59

    CAS  PubMed  Google Scholar 

  5. Berns KI, Kotin RM, Labow MA (1988) Regulation of adeno-associated virus DNA replication. Biochim Biophys Acta 951:425–429

    CAS  PubMed  Google Scholar 

  6. Russell DW, Alexander IE, Miller AD (1995) DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors. Proc Natl Acad Sci U S A 92:5719–5723

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Yakobson B, Hrynko TA, Peak MJ et al (1989) Replication of adeno-associated virus in cells irradiated with UV light at 254 nm. J Virol 63:1023–1030

    CAS  PubMed Central  PubMed  Google Scholar 

  8. King JA, Dubielzig R, Grimm D et al (2001) DNA helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids. EMBO J 20:3282–3291

    CAS  PubMed Central  PubMed  Google Scholar 

  9. McLaughlin SK, Collis P, Hermonat PL et al (1988) Adeno-associated virus general transduction vectors: analysis of proviral structures. J Virol 62:1963–1973

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Samulski RJ, Chang LS, Shenk T (1989) Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol 63:3822–3828

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Berns KI, Pinkerton TC, Thomas GF et al (1975) Detection of adeno-associated virus (AAV)-specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology 68:556–560

    CAS  PubMed  Google Scholar 

  12. Weinberg MS, Samulski RJ, McCown TJ (2012) Adeno-associated virus (AAV) gene therapy for neurological disease. Neuropharmacology 69:82–88

    PubMed  Google Scholar 

  13. Chirmule N, Propert K, Magosin S et al (1999) Immune responses to adenovirus and adeno-associated virus in humans. Gene Ther 6:1574–1583

    CAS  PubMed  Google Scholar 

  14. Kotin RM, Siniscalco M, Samulski RJ et al (1990) Site-specific integration by adeno-associated virus. Proc Natl Acad Sci U S A 87:2211–2215

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Samulski RJ, Zhu X, Xiao X et al (1991) Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 10:3941–3950

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Weitzman MD, Kyostio SR, Kotin RM et al (1994) Adeno-associated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA. Proc Natl Acad Sci U S A 91:5808–5812

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Balague C, Kalla M, Zhang WW (1997) Adeno-associated virus Rep78 protein and terminal repeats enhance integration of DNA sequences into the cellular genome. J Virol 71:3299–3306

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Cheung AK, Hoggan MD, Hauswirth WW et al (1980) Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J Virol 33:739–748

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Flannery JG, Zolotukhin S, Vaquero MI et al (1997) Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc Natl Acad Sci U S A 94:6916–6921

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Xiao X, Li J, Samulski RJ (1996) Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol 70:8098–8108

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Fisher KJ, Jooss K, Alston J et al (1997) Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med 3:306–312

    CAS  PubMed  Google Scholar 

  22. Ponnazhagan S, Mukherjee P, Yoder MC et al (1997) Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice. Gene 190:203–210

    CAS  PubMed  Google Scholar 

  23. Kaplitt MG, Leone P, Samulski RJ et al (1994) Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 8:148–154

    CAS  PubMed  Google Scholar 

  24. McCown TJ, Xiao X, Li J et al (1996) Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res 713:99–107

    CAS  PubMed  Google Scholar 

  25. Xiao X, Li J, McCown TJ et al (1997) Gene transfer by adeno-associated virus vectors into the central nervous system. Exp Neurol 144:113–124

    CAS  PubMed  Google Scholar 

  26. Li J, Wang D, Qian S et al (2003) Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors. Gene Ther 10:1807–1813

    CAS  PubMed  Google Scholar 

  27. Monahan PE, Samulski RJ, Tazelaar J et al (1998) Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dog model of hemophilia. Gene Ther 5:40–49

    CAS  PubMed  Google Scholar 

  28. Grieger JC, Samulski RJ (2012) Adeno-associated virus vectorology, manufacturing, and clinical applications. Methods Enzymol 507:229–254

    CAS  PubMed  Google Scholar 

  29. Harris JA, Devidze N, Verret L et al (2010) Transsynaptic progression of amyloid-beta-induced neuronal dysfunction within the entorhinal-hippocampal network. Neuron 68:428–441

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Wu Z, Asokan A, Grieger JC et al (2006) Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes. J Virol 80:11393–11397

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Samulski RJ, Berns KI, Tan M et al (1982) Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci U S A 79:2077–2081

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Burger C, Gorbatyuk OS, Velardo MJ et al (2004) Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 10:302–317

    CAS  PubMed  Google Scholar 

  33. Cearley CN, Wolfe JH (2006) Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain. Mol Ther 13:528–537

    CAS  PubMed  Google Scholar 

  34. Klein RL, Dayton RD, Tatom JB et al (2008) Tau expression levels from various adeno-associated virus vector serotypes produce graded neurodegenerative disease states. Eur J Neurosci 27:1615–1625

    PubMed Central  PubMed  Google Scholar 

  35. Choi VW, McCarty DM, Samulski RJ (2005) AAV hybrid serotypes: improved vectors for gene delivery. Curr Gene Ther 5:299–310

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Parks WP, Boucher DW, Melnick JL et al (1970) Seroepidemiological and ecological studies of the adenovirus-associated satellite viruses. Infect Immun 2:716–722

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Xiao W, Chirmule N, Berta SC et al (1999) Gene therapy vectors based on adeno-associated virus type 1. J Virol 73:3994–4003

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Zincarelli C, Soltys S, Rengo G et al (2008) Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 16:1073–1080

    CAS  PubMed  Google Scholar 

  39. Gao G, Vandenberghe LH, Alvira MR et al (2004) Clades of adeno-associated viruses are widely disseminated in human tissues. J Virol 78:6381–6388

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Klein RL, Dayton RD, Leidenheimer NJ et al (2006) Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins. Mol Ther 13:517–527

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Gray SJ, Matagne V, Bachaboina L et al (2011) Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. Mol Ther 19:1058–1069

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Dodiya HB, Bjorklund T, Stansell J 3rd et al (2010) Differential transduction following basal ganglia administration of distinct pseudotyped AAV capsid serotypes in nonhuman primates. Mol Ther 18:579–587

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Foust KD, Nurre E, Montgomery CL et al (2009) Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 27:59–65

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Bevan AK, Duque S, Foust KD et al (2011) Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther 19:1971–1980

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Dayton RD, Wang DB, Klein RL (2012) The advent of AAV9 expands applications for brain and spinal cord gene delivery. Expert Opin Biol Ther 12:757–766

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Allay JA, Sleep S, Long S et al (2011) Good manufacturing practice production of self-complementary serotype 8 adeno-associated viral vector for a hemophilia B clinical trial. Hum Gene Ther 22:595–604

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Masamizu Y, Okada T, Kawasaki K et al (2011) Local and retrograde gene transfer into primate neuronal pathways via adeno-associated virus serotype 8 and 9. Neuroscience 193:249–258

    CAS  PubMed  Google Scholar 

  48. Gray SJ, Blake BL, Criswell HE et al (2010) Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB). Mol Ther 18:570–578

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Bowles DE, McPhee SW, Li C et al (2012) Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 20:443–455

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Peel AL, Klein RL (2000) Adeno-associated virus vectors: activity and applications in the CNS. J Neurosci Methods 98:95–104

    CAS  PubMed  Google Scholar 

  51. Gray SJ, Foti SB, Schwartz JW et al (2011) Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors. Hum Gene Ther 22:1143–1153

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199

    CAS  PubMed  Google Scholar 

  53. Klein RL, Hamby ME, Gong Y et al (2002) Dose and promoter effects of adeno-associated viral vector for green fluorescent protein expression in the rat brain. Exp Neurol 176:66–74

    CAS  PubMed  Google Scholar 

  54. Chen H, McCarty DM, Bruce AT et al (1999) Oligodendrocyte-specific gene expression in mouse brain: use of a myelin-forming cell type-specific promoter in an adeno-associated virus. J Neurosci Res 55:504–513

    CAS  PubMed  Google Scholar 

  55. Feng X, Eide FF, Jiang H et al (2004) Adeno-associated viral vector-mediated ApoE expression in Alzheimer’s disease mice: low CNS immune response, long-term expression, and astrocyte specificity. Front Biosci 9:1540–1546

    CAS  PubMed  Google Scholar 

  56. Lawlor PA, Bland RJ, Mouravlev A et al (2009) Efficient gene delivery and selective transduction of glial cells in the mammalian brain by AAV serotypes isolated from nonhuman primates. Mol Ther 17:1692–1702

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Loeb JE, Cordier WS, Harris ME et al (1999) Enhanced expression of transgenes from adeno-associated virus vectors with the woodchuck hepatitis virus posttranscriptional regulatory element: implications for gene therapy. Hum Gene Ther 10:2295–2305

    CAS  PubMed  Google Scholar 

  58. Yan Z, Zhang Y, Duan D et al (2000) Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy. Proc Natl Acad Sci U S A 97:6716–6721

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Daya S, Berns KI (2008) Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 21:583–593

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Xiao X, Li J, Samulski RJ (1998) Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 72:2224–2232

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Grimm D, Kern A, Rittner K et al (1998) Novel tools for production and purification of recombinant adeno-associated virus vectors. Hum Gene Ther 9:2745–2760

    CAS  PubMed  Google Scholar 

  62. Grimm D, Kay MA, Kleinschmidt JA (2003) Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol Ther 7:839–850

    CAS  PubMed  Google Scholar 

  63. Zolotukhin S, Byrne BJ, Mason E et al (1999) Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther 6:973–985

    CAS  PubMed  Google Scholar 

  64. Summerford C, Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72:1438–1445

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Halbert CL, Allen JM, Miller AD (2001) Adeno-associated virus type 6 (AAV6) vectors mediate efficient transduction of airway epithelial cells in mouse lungs compared to that of AAV2 vectors. J Virol 75:6615–6624

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Tuszynski MH, Thal L, Pay M et al (2005) A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11:551–555

    CAS  PubMed  Google Scholar 

  67. Mandel RJ (2010) CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer’s disease. Curr Opin Mol Ther 12:240–247

    CAS  PubMed  Google Scholar 

  68. Wu K, Meyer EM, Bennett JA et al (2005) AAV2/5-mediated NGF gene delivery protects septal cholinergic neurons following axotomy. Brain Res 1061:107–113

    CAS  PubMed  Google Scholar 

  69. Gene Therapy Clinical Trials Worldwide (2014), http://www.abedia.com/wiley/. John Wiley & Sons, Ltd

  70. Bobo RH, Laske DW, Akbasak A et al (1994) Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A 91:2076–2080

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Bankiewicz KS, Eberling JL, Kohutnicka M et al (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164:2–14

    CAS  PubMed  Google Scholar 

  72. Krauze MT, Saito R, Noble C et al (2005) Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J Neurosurg 103:923–929

    PubMed  Google Scholar 

  73. Towne C, Schneider BL, Kieran D et al (2010) Efficient transduction of non-human primate motor neurons after intramuscular delivery of recombinant AAV serotype 6. Gene Ther 17:141–146

    CAS  PubMed  Google Scholar 

  74. Schenk D, Barbour R, Dunn W et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177

    CAS  PubMed  Google Scholar 

  75. Morgan D, Diamond DM, Gottschall PE et al (2000) A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 408:982–985

    CAS  PubMed  Google Scholar 

  76. Callaway E (2012) Alzheimer’s drugs take a new tack. Nature 489:13–14

    CAS  PubMed  Google Scholar 

  77. Games D, Adams D, Alessandrini R et al (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373:523–527

    CAS  PubMed  Google Scholar 

  78. Hsiao K, Chapman P, Nilsen S et al (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102

    CAS  PubMed  Google Scholar 

  79. Yoshiyama Y, Higuchi M, Zhang B et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351

    CAS  PubMed  Google Scholar 

  80. de Calignon A, Polydoro M, Suarez-Calvet M et al (2012) Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron 73:685–697

    PubMed Central  PubMed  Google Scholar 

  81. Grueninger F, Bohrmann B, Czech C et al (2010) Phosphorylation of Tau at S422 is enhanced by Abeta in TauPS2APP triple transgenic mice. Neurobiol Dis 37:294–306

    CAS  PubMed  Google Scholar 

  82. West MJ, Gundersen HJ (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296:1–22

    CAS  PubMed  Google Scholar 

  83. Sze CI, Troncoso JC, Kawas C et al (1997) Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol 56:933–944

    CAS  PubMed  Google Scholar 

  84. Arendash GW, King DL, Gordon MN et al (2001) Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes. Brain Res 891:42–53

    CAS  PubMed  Google Scholar 

  85. Kiyota T, Yamamoto M, Schroder B et al (2009) AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol Ther 17:803–809

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Kiyota T, Ingraham KL, Swan RJ et al (2012) AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP + PS1 mice. Gene Ther 19:724–733

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Hsia AY, Masliah E, McConlogue L et al (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc Natl Acad Sci U S A 96:3228–3233

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Chapman PF, White GL, Jones MW et al (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2:271–276

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  90. Terry RD, Masliah E, Salmon DP et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580

    CAS  PubMed  Google Scholar 

  91. Galvan V, Bredesen DE (2007) Neurogenesis in the adult brain: implications for Alzheimer’s disease. CNS Neurol Disord Drug Targets 6:303–310

    CAS  PubMed  Google Scholar 

  92. Abdipranoto A, Wu S, Stayte S et al (2008) The role of neurogenesis in neurodegenerative diseases and its implications for therapeutic development. CNS Neurol Disord Drug Targets 7:187–210

    CAS  PubMed  Google Scholar 

  93. Biscaro B, Lindvall O, Hock C et al (2009) Abeta immunotherapy protects morphology and survival of adult-born neurons in doubly transgenic APP/PS1 mice. J Neurosci 29:14108–14119

    CAS  PubMed  Google Scholar 

  94. Kiyota T, Okuyama S, Swan RJ et al (2010) CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer’s disease-like pathogenesis in APP + PS1 bigenic mice. FASEB J 24:3093–3102

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Hefti F (1986) Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci 6:2155–2162

    CAS  PubMed  Google Scholar 

  96. Bishop KM, Hofer EK, Mehta A et al (2008) Therapeutic potential of CERE-110 (AAV2-NGF): targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons. Exp Neurol 211:574–584

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Arvanitakis ZPS, Bartus RT, Bennett D (2007) A phase I clinical trial of CERE-110 (AAV-NGF) gene delivery in Alzheimer's disease. American Academy of Neurology Annual Meeting, Boston, MA

    Google Scholar 

  98. Rafii MS, Baumann TL, Bakay RA et al (2014) A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease. Alzheimer’s Dement 10(5):571–581

    Google Scholar 

  99. Nagahara AH, Merrill DA, Coppola G et al (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 15:331–337

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Mudo G, Bonomo A, Di Liberto V et al (2009) The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain. J Neural Transm 116:995–1005

    CAS  PubMed  Google Scholar 

  101. Kuhn HG, Winkler J, Kempermann G et al (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17:5820–5829

    CAS  PubMed  Google Scholar 

  102. Tao Y, Black IB, DiCicco-Bloom E (1997) In vivo neurogenesis is inhibited by neutralizing antibodies to basic fibroblast growth factor. J Neurobiol 33:289–296

    CAS  PubMed  Google Scholar 

  103. Jin K, Sun Y, Xie L et al (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2:175–183

    CAS  PubMed  Google Scholar 

  104. Baldauf K, Reymann KG (2005) Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia. Brain Res 1056:158–167

    CAS  PubMed  Google Scholar 

  105. Kiyota T, Ingraham KL, Jacobsen MT et al (2011) FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer’s disease and has therapeutic implications for neurocognitive disorders. Proc Natl Acad Sci U S A 108:E1339–E1348

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Arendash GW, Gordon MN, Diamond DM et al (2001) Behavioral assessment of Alzheimer’s transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory. DNA Cell Biol 20:737–744

    CAS  PubMed  Google Scholar 

  107. Westermark GT, Johnson KH, Westermark P (1999) Staining methods for identification of amyloid in tissue. Methods Enzymol 309:3–25

    CAS  PubMed  Google Scholar 

  108. Selkoe DJ (2009) Thioflavin-S staining protocol. http://www.alzforum.org/sites/default/files/protocol_Thioflavin_S_staining_of_brain_tissue.pdf. Accessed 16 Nov 2014

  109. Guo P, El-Gohary Y, Prasadan K et al (2012) Rapid and simplified purification of recombinant adeno-associated virus. J Virol Methods 183:139–146

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Miyake K, Miyake N, Yamazaki Y et al (2012) Serotype-independent method of recombinant adeno-associated virus (AAV) vector production and purification. J Nippon Med Sch 79:394–402

    CAS  PubMed  Google Scholar 

  111. Wu Z, Miller E, Agbandje-McKenna M et al (2006) Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. J Virol 80:9093–9103

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Stroes ES, Nierman MC, Meulenberg JJ et al (2008) Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol 28:2303–2304

    CAS  PubMed  Google Scholar 

  113. Takeda S, Takahashi M, Mizukami H et al (2004) Successful gene transfer using adeno-associated virus vectors into the kidney: comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo. Nephron Exp Nephrol 96:e119–e126

    CAS  PubMed  Google Scholar 

  114. Maguire AM, High KA, Auricchio A et al (2009) Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet 374:1597–1605

    CAS  PubMed  Google Scholar 

  115. Davidson BL, Stein CS, Heth JA et al (2000) Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci U S A 97:3428–3432

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Akache B, Grimm D, Pandey K et al (2006) The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9. J Virol 80:9831–9836

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Qing K, Mah C, Hansen J et al (1999) Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med 5:71–77

    CAS  PubMed  Google Scholar 

  118. Summerford C, Bartlett JS, Samulski RJ (1999) AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med 5:78–82

    CAS  PubMed  Google Scholar 

  119. Asokan A, Hamra JB, Govindasamy L et al (2006) Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. J Virol 80:8961–8969

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Kashiwakura Y, Tamayose K, Iwabuchi K et al (2005) Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. J Virol 79:609–614

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Glushakova LG, Lisankie MJ, Eruslanov EB et al (2009) AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells. Mol Genet Metab 98:289–299

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Hadaczek P, Eberling JL, Pivirotto P et al (2010) Eight years of clinical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol Ther 18:1458–1461

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Mease PJ, Hobbs K, Chalmers A et al (2009) Local delivery of a recombinant adeno-associated vector containing a tumour necrosis factor alpha antagonist gene in inflammatory arthritis: a phase 1 dose-escalation safety and tolerability study. Ann Rheum Dis 68:1247–1254

    CAS  PubMed  Google Scholar 

  124. Rabinowitz JE, Rolling F, Li C et al (2002) Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J Virol 76:791–801

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Ling C, Lu Y, Kalsi JK et al (2010) Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3. Hum Gene Ther 21:1741–1747

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Weber M, Rabinowitz J, Provost N et al (2003) Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. Mol Ther 7:774–781

    CAS  PubMed  Google Scholar 

  127. Kaludov N, Brown KE, Walters RW et al (2001) Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75:6884–6893

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Walters RW, Yi SM, Keshavjee S et al (2001) Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer. J Biol Chem 276:20610–20616

    CAS  PubMed  Google Scholar 

  129. Di Pasquale G, Davidson BL, Stein CS et al (2003) Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9:1306–1312

    PubMed  Google Scholar 

  130. Adriaansen J, Khoury M, de Cortie CJ et al (2007) Reduction of arthritis following intra-articular administration of an adeno-associated virus serotype 5 expressing a disease-inducible TNF-blocking agent. Ann Rheum Dis 66:1143–1150

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Weller ML, Amornphimoltham P, Schmidt M et al (2010) Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6. Nat Med 16:662–664

    CAS  PubMed Central  PubMed  Google Scholar 

  132. Gao GP, Alvira MR, Wang L et al (2002) Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A 99:11854–11859

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Fang H, Lai NC, Gao MH et al (2012) Comparison of Adeno-Associated Virus Serotypes and Delivery Methods for Cardiac Gene Transfer. Hum Gene Ther Methods 23(4):234–241

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Blankinship MJ, Gregorevic P, Allen JM et al (2004) Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Mol Ther 10:671–678

    CAS  PubMed  Google Scholar 

  135. Shen S, Bryant KD, Brown SM et al (2011) Terminal N-linked galactose is the primary receptor for adeno-associated virus 9. J Biol Chem 286:13532–13540

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Mori S, Takeuchi T, Enomoto Y et al (2008) Tissue distribution of cynomolgus adeno-associated viruses AAV10, AAV11, and AAVcy.7 in naturally infected monkeys. Arch Virol 153:375–380

    CAS  PubMed  Google Scholar 

  137. Anderson SM, Famous KR, Sadri-Vakili G et al (2008) CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking. Nat Neurosci 11:344–353

    CAS  PubMed  Google Scholar 

  138. Quinn K, Quirion MR, Lo CY et al (2011) Intranasal administration of adeno-associated virus type 12 (AAV12) leads to transduction of the nasal epithelia and can initiate transgene-specific immune response. Mol Ther 19:1990–1998

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapeutics and Graduate Program in Neuroscience, Boston University School of Medicine, Boston, MA, USA

    Maya Woodbury & Tsuneya Ikezu

  2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

    Tomomi Kiyota

  3. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    Tsuneya Ikezu

  4. Laboratory of Molecular NeuroTherapeutics, Department of Pharmacology and Experimental Therapeutics and Neurology, Boston University School of Medicine, 72 East Concord Street, L-606B, Boston, MA, 02118, USA

    Tsuneya Ikezu

Authors
  1. Maya Woodbury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomomi Kiyota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsuneya Ikezu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tsuneya Ikezu .

Editor information

Editors and Affiliations

  1. Queen Mary University of London, London, United Kingdom

    Xuenong Bo

  2. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    Joost Verhaagen

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Woodbury, M., Kiyota, T., Ikezu, T. (2015). Gene Delivery and Gene Therapy for Alzheimer’s Disease. In: Bo, X., Verhaagen, J. (eds) Gene Delivery and Therapy for Neurological Disorders. Neuromethods, vol 98. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2306-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2306-9_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2305-2

  • Online ISBN: 978-1-4939-2306-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation