Adult Neurogenesis in Neurodegenerative Diseases

  • Tomas Deierborg
  • Jia- Yi Li
  • Patrik Brundin

Neurogenesis occurs in the adult hippocampus and subventricular zone. It provides an exciting potential inroad to new treatments for slow neurodegenerative disorders. Changes in neurogenesis in human degenerative diseases may also teach us something about the underlying disease mechanisms. In the present chapter, we review data from clinical and experimental studies concerning neurogenesis in Alzheimer’s, Huntington’s and Parkinson’s diseases. In brief, the clinical data have not clearly shown whether the rate of neurogenesis is changed by the pathogenesis in these three diseases. Whether neurogenesis occurs at all in the adult substantia nigra under baseline conditions remains controversial. Studies on animal models of the three neurodegenerative conditions provide a mixed picture, with disease/ damage to the brain being associated both decreases and increases in neurogenesis in the different studied brain regions. In conclusion, this exciting research field is still in its infancy. It is too early to say whether neurogenesis in the adult brain can be targeted by novel therapies and be used to reduce functional deficits in slow neurodegenerative diseases.


Substantia Nigra Dentate Gyrus Neural Stem Cell Adult Neurogenesis Hippocampal Neurogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Altman, J., 1962, Are new neurons formed in the brains of adult mammals? Science 135: 1127.CrossRefPubMedGoogle Scholar
  2. Alvarez-Buylla, A. and Lim, D.A., 2004, For the long run: maintaining germinal niches in the adult brain. Neuron 41: 683.CrossRefPubMedGoogle Scholar
  3. Ambrogini, P., Orsini, L., Mancini, C., Ferri, P., Ciaroni, S. and Cuppini, R., 2004, Learning may reduce neurogenesis in adult rat dentate gyrus. Neurosci. Lett. 359: 13.CrossRefPubMedGoogle Scholar
  4. Bedard, A. and Parent, A., 2004, Evidence of newly generated neurons in the human olfactory bulb. Brain Res. Dev. Brain Res. 151: 159.CrossRefGoogle Scholar
  5. Birks, J., 2006, Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst. Rev. 1: CD005593Google Scholar
  6. Bondolfi, L., Calhoun, M., Ermini, F., Kuhn, H.G., Wiederhold, K.H., Walker, L., Staufenbiel, M. and Jucker, M., 2002, Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J. Neurosci. 22: 515.PubMedGoogle Scholar
  7. Busser, J., Geldmacher, D.S. and Herrup, K., 1998, Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J. Neurosci. 18: 2801.PubMedGoogle Scholar
  8. Caille, I., Allinquant, B., Dupont, E., Bouillot, C., Langer, A., Muller, U. and Prochiantz, A., 2004, Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Development 131: 2173.CrossRefPubMedGoogle Scholar
  9. Carlen, M., Cassidy, R.M., Brismar, H., Smith, G.A., Enquist, L.W. and Frisen, J., 2002, Functional integration of adult-born neurons. Curr. Biol. 12: 606.CrossRefPubMedGoogle Scholar
  10. Chaudhury, A.R., Gerecke, K.M., Wyss, J.M., Morgan, D.G., Gordon, M.N. and Carroll, S.L., 2003, Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J. Neuropathol. Exp. Neurol. 62: 42.PubMedGoogle Scholar
  11. Chen, Y., Ai, Y., Slevin, J.R., Maley, B.E. and Gash, D.M., 2005, Progenitor proliferation in the adult hippocampus and substantia nigra induced by glial cell line-derived neurotrophic factor. Exp. Neurol. 196: 87.CrossRefPubMedGoogle Scholar
  12. Chevallier, N.L., Soriano, S., Kang, D.E., Masliah, E., Hu, G. and Koo, E.H., 2005, Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am. J. Pathol. 167: 151.PubMedGoogle Scholar
  13. Ciechanover, A. and Brundin, P., 2003, The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron 40: 427.CrossRefPubMedGoogle Scholar
  14. Cooper, O. and Isacson, O., 2004, Intrastriatal transforming growth factor alpha delivery to a model of Parkinson’s disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons. J. Neurosci. 24: 8924.CrossRefPubMedGoogle Scholar
  15. Csernansky, J.G., Wang, L., Joshi, S., Miller, J.P., Gado, M., Kido, D., McKeel, D., Morris, J.C. and Miller, M.I., 2000, Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type. Neurology 55: 1636.PubMedGoogle Scholar
  16. Curtis, M.A., Penney, E.B., Pearson, A.G., van Roon-Mom, W.M., Butterworth, N.J., Dragunow, M., Connor, B. and Faull, R.L., 2003, Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc. Natl Acad. Sci. USA 100: 9023.CrossRefPubMedGoogle Scholar
  17. Curtis, M.A., Penney, E.B., Pearson, J., Dragunow, M., Connor, B. and Faull, R.L., 2005, The distribution of progenitor cells in the subependymal layer of the lateral ventricle in the normal and Huntington’s disease human brain. Neuroscience 132: 777.CrossRefPubMedGoogle Scholar
  18. Dodart, J.C., Mathis, C., Saura, J., Bales, K.R., Paul, S.M. and Ungerer, A., 2000, Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice. Neurobiol. Dis. 7: 71.CrossRefPubMedGoogle Scholar
  19. Dong, H., Goico, B., Martin, M., Csernansky, C.A., Bertchume, A. and Csernansky, J.G., 2004, Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 127: 601.CrossRefPubMedGoogle Scholar
  20. Donovan, M.H., Yazdani, U., Norris, R.D., Games, D., German, D.C. and Eisch, A.J., 2006, Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. J. Comp. Neurol. 495: 70.CrossRefPubMedGoogle Scholar
  21. Erbayrahar, S., Grasso, G., Sfacteria, A., Xie, Q.W., Coleman, T., Kreilgaard, M., Torup, L., Sager, T., Erbayraktar, Z., Gokmen, N., Yilmaz, O., Ghezzi, P., Villa, P., Fratelli, M., Casagrande, S., Leist, M., Helboe, L., Gerwein, J., Christensen, S., Geist, M.A. , Pedersen, L.O., Cerami-Hand, C., Wuerth, J.P., Cerami, A. and Brines, M., 2003, Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc. Natl Acad. Sci. USA 100: 6741.CrossRefGoogle Scholar
  22. Eriksdotter Jonhagen, M., Nordberg, A., Amberla, K., Backman, L., Ebendal, T., Meyerson, B., Olson, L., Seiger Shigeta, M., Theodorsson, E., Viitanen, M., Winblad, B. and Wahlund, L.O., 1998, Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 9: 246.CrossRefPubMedGoogle Scholar
  23. Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A. and Gage. F.H., 1998, Neurogenesis in the adult human hippocampus. Nat. Med. 4: 1313.CrossRefPubMedGoogle Scholar
  24. Evans, D.A., Funkenstein, H.H., Albert, M.S., Scherr, P.A., Cook, N.R., Chown, M.J., Hebert, L.E., Hennekens, C.H. and Taylor, J.O., 1989, Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 262: 2551.CrossRefPubMedGoogle Scholar
  25. Fahn, S., 1989, The history of parkinsonism. Mov. Disord. 4 (Suppl. 1): S2.CrossRefPubMedGoogle Scholar
  26. Feng, R., Rampon, C., Tang, Y.P., Shrom, D., Jin, J., Kyin, M., Sopher, B., Miller, M.W., Ware, C.B., Martin, G.M., Kim, S.H., Langdon, R.B., Sisodia, S.S. and Tsien, J.Z., 2001, Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32: 911.CrossRefPubMedGoogle Scholar
  27. Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E. and Scazufca, M., 2005, Global prevalence of dementia: a Delphi consensus study. Lancet 366: 2112.CrossRefPubMedGoogle Scholar
  28. Frielingsdorf, H., Schwarz, K., Brundin, P. and Mohapel, P., 2004, No evidence for new dopaminergic neurons in the adult mammalian substantia nigra. Proc. Natl Acad. Sci. USA 101: 10177.CrossRefPubMedGoogle Scholar
  29. Gil, J.M., Leist, M., Popovic, N., Brundin, P. and Petersen, A., 2004, Asialoerythropoietin is not effective in the R6/2 line of Huntington’s disease mice. BMC Neurosci. 5: 17.CrossRefPubMedGoogle Scholar
  30. Gil, J.M., Mohapel, P., Araujo, I.M., Popovic, N., Li, J.Y., Brundin, P. and Petersen, A., 2005, Reduced hippocampal neurogenesis in R6/2 transgenic Huntington’s disease mice. Neurobiol. Dis. 20: 744.CrossRefPubMedGoogle Scholar
  31. Gould, E., Beylin, A., Tanapat, P., Reeves, A. and Shors, T.J., 1999, Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2: 260.CrossRefPubMedGoogle Scholar
  32. Gouras, G.K., Almeida, C.G. and Takahashi, R.H., 2005, Intraneuronal Abeta accumulation and origin of plaques in Alzheimer’s disease. Neurobiol. Aging 26: 1235.CrossRefPubMedGoogle Scholar
  33. Hack, M.A., Saghatelyan, A., de Chevigny, A., Pfeifer, A., Ashery-Padan, R., Lledo, P.M. and Gotz, M., 2005 Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 8: 865.PubMedGoogle Scholar
  34. Handler, M., Yang, X. and Shen, J., 2000, Presenilin-1 regulates neuronal differentiation during neurogenesis. Development 127: 2593.PubMedGoogle Scholar
  35. Harper, P.S., 1996, Huntington’s Disease. W.B. Saunders, London.Google Scholar
  36. Haughey, N.J., Liu, D., Nath, A., Borchard, A.C. and Mattson, M.P., 2002, Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid β-peptide: implications for the pathogenesis of Alzheimer’s disease. Neuromol. Med. 1: 125.CrossRefGoogle Scholar
  37. Higgins, G.A. and Jacobsen, H., 2003, Transgenic mouse models of Alzheimer’s disease: phenotype and application. Behav. Pharmacol. 14: 419.PubMedGoogle Scholar
  38. Holscher, C., 2003, Time, space and hippocampal functions. Rev. Neurosci. 14: 253.PubMedGoogle Scholar
  39. Honda, S., Itoh, F., Yoshimoto, M., Ohno, S., Hinoda, Y. and Imai, K., 2000, Association between complement regulatory protein factor H and AM34 antigen, detected in senile plaques. J. Gerontol. A Biol. Sci. Med. Sci. 55: M265.PubMedGoogle Scholar
  40. Jin, K., Galvan, V., Xie, L., Mao, X.O., Gorostiza, O.F., Bredesen, D.E. and Greenberg, D.A., 2004a, Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw,Ind) mice. Proc. Natl Acad. Sci. USA 101: 13363.CrossRefPubMedGoogle Scholar
  41. Jin, K., Peel, A.L., Mao, X.O., Xie, L., Cottrell, B.A., Henshall, D.C. and Greenberg, D.A., 2004b, Increased hippocampal neurogenesis in Alzheimer’s disease. Proc. Natl Acad. Sci. USA 101: 343.CrossRefPubMedGoogle Scholar
  42. Jin, K., LaFevre-Bernt, M., Sun, Y., Chen, S., Gafni, J., Crippen, D., Logvinova, A., Ross, C.A., Greenberg, D.A. and Ellerby, L.M., 2005, FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington’s disease. Proc. Natl Acad. Sci. USA 102: 18189.CrossRefPubMedGoogle Scholar
  43. Jin, K., Xie, L., Mao, X.O. and Greenberg, D.A., 2006, Alzheimer’s disease drugs promote neurogenesis. Brain Res. 1085: 183.CrossRefPubMedGoogle Scholar
  44. Katchanov, J., Harms, C., Gertz, K., Hauck, L., Waeber, C., Hirt, L., Priller, J., von Harsdorf, R., Bruck, W., Hortnagl, H., Dirnagl, U., Bhide, P.G. and Endres, M., 2001, Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. J. Neurosci. 21: 5045.PubMedGoogle Scholar
  45. Kay, J.N. and Blum, M., 2000, Differential response of ventral midbrain and striatal progenitor cells to lesions of the nigrostriatal dopaminergic projection. Dev. Neurosci. 22: 56.CrossRefPubMedGoogle Scholar
  46. Kempermann, G., 2006, Adult Neurogenesis, Stem Cells and Neuronal Development in the Adult Brain. Oxford University Press, New York.Google Scholar
  47. Kempermann, G., Jessberger, S., Steiner, B. and Kronenberg, G., 2004, Milestones of neuronal development in the adult hippocampus. Trends Neurosci. 27: 447.CrossRefPubMedGoogle Scholar
  48. Kornack, D.R. and Rakic, P., 2001, The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc. Natl Acad. Sci. USA 98: 4752.CrossRefPubMedGoogle Scholar
  49. Kremer, H.P., Roos, R.A., Dingjan, G., Marani, E. and Bots, G.T., 1990, Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J. Neuropathol. Exp. Neurol. 49: 371.CrossRefPubMedGoogle Scholar
  50. Kremer, H.P., Roos, R.A., Dingjan, G.M., Bots, G.T., Bruyn, G.W. and Hofman, M.A., 1991, The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington’s disease. Neurosci. Lett. 132: 101.CrossRefPubMedGoogle Scholar
  51. Kuhn, H.G., Dickinson-Anson, H. and Gage, F.H., 1996, Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16: 2027.PubMedGoogle Scholar
  52. Laakso, M.P., Soininen, H., Partanen, K., Helkala, E.L., Hartikainen, P., Vainio, P., Hallikainen, M., Hanninen, T. and Riekkinen, P.J., Sr., 1995, Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer’s disease: correlation with memory functions. J. Neural Transm. Park. Dis. Dement. Sect. 9: 73.CrossRefPubMedGoogle Scholar
  53. Landles, C. and Bates, G.P., 2004, Huntingtin and the molecular pathogenesis of Huntington’s disease. EMBO Rep. 5: 958.CrossRefPubMedGoogle Scholar
  54. Lazic, S.E., Grote, H., Armstrong, R.J., Blakemore, C., Hannan, A.J., van Dellen, A. and Barker, R.A., 2004, Decreased hippocampal cell proliferation in R6/1 Huntington’s mice. Neuroreport 15: 811.CrossRefPubMedGoogle Scholar
  55. Lazic, S.E., Grote, H.E., Blakemore, C., Hannan, A.J., van Dellen, A., Phillips, W. and Barker, R.A., 2006, Neurogenesis in the R6/1 transgenic mouse model of Huntington’s disease: effects of environmental enrichment. Eur. J. Neurosci. 23: 1829.CrossRefPubMedGoogle Scholar
  56. Lemere, C.A., Maier, M., Jiang, L., Peng, Y. and Seabrook, T.J., 2006, Amyloid-β immunotherapy for the prevention and treatment of Alzheimer disease: lessons from mice, monkeys, and humans. Rejuvenation Res. 9: 77.CrossRefPubMedGoogle Scholar
  57. Leuner, B., Gould, E. and Shors, T.J., 2006, Is there a link between adult neurogenesis and learning? Hippocampus 16: 216.CrossRefPubMedGoogle Scholar
  58. Li, S.H., Yu, Z.X., Li, C.L., Nguyen, H.P., Zhou, Y.X., Deng, C. and Li, X.J., 2003, Lack of huntingtin-associated protein-1 causes neuronal death resembling hypothalamic degeneration in Huntington’s disease. J. Neurosci. 23: 6956.PubMedGoogle Scholar
  59. Lie, D.C., Dziewczapolski, G., Willhoite, A.R., Kaspar, B.K., Shults, C.W. and Gage, F.H., 2002, The adult substantia nigra contains progenitor cells with neurogenic potential. J. Neurosci. 22: 6639.PubMedGoogle Scholar
  60. Liu, M., Pleasure, S.J., Collins, A.E., Noebels, J.L., Naya, F.J., Tsai, M.J. and Lowenstein, D.H., 2000, Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc. Natl Acad. Sci. USA 97: 865.CrossRefPubMedGoogle Scholar
  61. Lledo, P.M. and Saghatelyan, A., 2005, Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience. Trends Neurosci. 28: 248.CrossRefPubMedGoogle Scholar
  62. Lopez-Toledano, M.A. and Shelanski, M.L., 2004, Neurogenic effect of β-amyloid peptide in the development of neural stem cells. J. Neurosci. 24: 5439.CrossRefPubMedGoogle Scholar
  63. Lyness, S.A., Zarow, C. and Chui, H.C., 2003, Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis. Neurobiol. Aging 24: 1.CrossRefPubMedGoogle Scholar
  64. Marcora, E., Gowan, K. and Lee, J.E., 2003, Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2. Proc. Natl Acad. Sci. USA 100: 9578.CrossRefPubMedGoogle Scholar
  65. Mohapel, P. and Brundin, P., 2004, Harnessing endogenous stem cells to treat neurodegenerative disorders of the basal ganglia. Parkinsonism Relat. Disord. 10: 259.CrossRefPubMedGoogle Scholar
  66. Murphy, D.G., DeCarli, C.D., Daly, E., Gillette, J.A., McIntosh, A.R., Haxby, J.V., Teichberg, D., Schapiro, M.B., Rapoport, S.I. and Horwitz, B., 1993, Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: correlations with disease severity. Biol. Psychiatry 34: 612.CrossRefPubMedGoogle Scholar
  67. Nagy, Z., 2000, Cell cycle regulatory failure in neurones: causes and consequences. Neurobiol. Aging 21: 761.CrossRefPubMedGoogle Scholar
  68. Nagy, Z., Esiri, M.M., Cato, A.M. and Smith, A.D., 1997a, Cell cycle markers in the hippocampus in Alzheimer’s disease. Acta Neuropathol. (Berl.) 94: 6.CrossRefGoogle Scholar
  69. Nagy, Z., Esiri, M.M. and Smith, A.D., 1997b, Expression of cell division markers in the hippocampus in Alzheimer’s disease and other neurodegenerative conditions. Acta Neuropathol. (Berl.) 93: 294.CrossRefGoogle Scholar
  70. Ohsawa, I., Takamura, C., Morimoto, T., Ishiguro, M. and Kohsaka, S., 1999, Amino-terminal region of secreted form of amyloid precursor protein stimulates proliferation of neural stem cells. Eur. J. Neurosci. 11:1907.CrossRefPubMedGoogle Scholar
  71. Pearson, H., 2006, Stem-cell tagging shows flaws. Nature 439: 519.CrossRefPubMedGoogle Scholar
  72. Petersen, A., Gil, J., Maat-Schieman, M.L., Bjorkqvist, M., Tanila, H., Araujo, I.M., Smith, R., Popovic, N., Wierup, N., Norlen, P., Li, J.Y., Roos, R.A., Sundler, F., Mulder, H. and Brundin, P., 2005, Orexin loss in Huntington’s disease. Hum. Mol. Genet. 14: 39.CrossRefPubMedGoogle Scholar
  73. Pietrzik, C. and Behl, C., 2005, Concepts for the treatment of Alzheimer’s disease: molecular mechanisms and clinical application. Int. J. Exp. Pathol. 86: 173.CrossRefPubMedGoogle Scholar
  74. Qin, Z.H., Wang, Y., Sapp, E., Cuiffo, B., Wanker, E., Hayden, M.R., Kegel, K.B., Aronin, N. and DiFiglia, M., 2004, Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J. Neurosci. 24: 269.CrossRefPubMedGoogle Scholar
  75. Rozemuller, J.M., Stam, F.C. and Eikelenboom, P., 1990, Acute phase proteins are present in amorphous plaques in the cerebral but not in the cerebellar cortex of patients with Alzheimer’s disease. Neurosci. Lett. 119: 75.CrossRefPubMedGoogle Scholar
  76. Sanai, N., Tramontin, A.D., Quinones-Hinojosa, A., Barbaro, N.M., Gupta, N., Kunwar, S., Lawton, M.T., McDermott, M.W., Parsa, A.T., Manuel-Garcia Verdugo, J., Berger, M.S. and Alvarez-Buylla, A., 2004, Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427: 740.CrossRefPubMedGoogle Scholar
  77. Shan, X., Chi, L., Bishop, M., Luo, C., Lien, L., Zhang, Z. and Liu, R., 2006, Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia nigra of MPTP-induced Parkinson’s disease-like mice. Stem Cells 24: 1280.CrossRefPubMedGoogle Scholar
  78. Steiner, B., Winter, C., Hosman, K., Siebert, E., Kempermann, G. and Kupsch, A., 2005, Enriched environment induces cellular plasticity in the adult substantia nigra and improves motor behavior function in the 6-OHDA rat model of Parkinson’s disease. Exp. Neurol. 199: 291.CrossRefPubMedGoogle Scholar
  79. St George-Hyslop, P.H., 2000, Molecular genetics of Alzheimer’s disease. Biol. Psychiatry 47: 183.CrossRefPubMedGoogle Scholar
  80. Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.H., Mistl, C., Rothacher, S., Ledermann, B, Burki, K., Frey, P., Paganetti, P.A., Waridel, C., Calhoun, M.E., Jucker, M., Probst, A., Staufenbiel, M. and Sommer, B., 1997, Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl Acad. Sci. USA 94: 13287.CrossRefPubMedGoogle Scholar
  81. Tanzi, R.E. and Bertram, L., 2005, Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120: 545.CrossRefPubMedGoogle Scholar
  82. Tatebayashi, Y., Lee, M.H., Li, L., Iqbal, K. and Grundke-Iqbal, I., 2003, The dentate gyrus neurogenesis: a therapeutic target for Alzheimer’s disease. Acta Neuropathol. (Berl.) 105: 225.Google Scholar
  83. Tuszynski, M.H., Thal, L., Pay, M., Salmon, D.P.U.H.S., Bakay, R., Patel, P., Blesch, A., Vahlsing, H.L., Ho, G., Tong, G., Potkin, S.G., Fallon, J., Hansen, L., Mufson, E.J., Kordower, J.H., Gall, C. and Conner, J., 2005, A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat. Med. 11: 551.CrossRefPubMedGoogle Scholar
  84. Van der Borght, K., Wallinga, A.E., Luiten, P.G., Eggen, B.J. and Van der Zee, E.A., 2005, Morris water maze learning in two rat strains increases the expression of the polysialylated form of the neural cell adhesion molecule in the dentate gyrus but has no effect on hippocampal neurogenesis. Behav. Neurosci. 119: 926.CrossRefPubMedGoogle Scholar
  85. Van kampen, J.M. and Eckman, C.B., 2006, Dopamine D3 receptor agonist delivery to a model of Parkinson’s disease restores the nigrostriatal pathway and improves locomotor behaviour. J. Neurosci. 26: 7272.CrossRefPubMedGoogle Scholar
  86. Van Kampen, J.M. and Robertson, H.A., 2005, A possible role for dopamine D3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra. Neuroscience 136: 381.CrossRefPubMedGoogle Scholar
  87. van Praag, H., Kempermann, G. and Gage, F.H., 1999, Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2: 266.CrossRefPubMedGoogle Scholar
  88. Verbeek, M.M., Otte-Holler, I., Wesseling, P., Ruiter, D.J. and de Waal, R.M., 1996, Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the A β-containing lesions in brains of patients with dementia of the Alzheimer type. Acta Neuropathol. (Berl.) 91: 608.Google Scholar
  89. Vincent, I., Jicha, G., Rosado, M. and Dickson, D.W., 1997, Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer’s disease brain. J. Neurosci. 17: 3588.PubMedGoogle Scholar
  90. Vonsattel, J.P. and DiFiglia, M., 1998, Huntington disease. J. Neuropathol. Exp. Neurol. 57: 369.CrossRefPubMedGoogle Scholar
  91. Wang, R., Dineley, K.T., Sweatt, J.D. and Zheng, H., 2004, Presenilin 1 familial Alzheimer’s disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience 126: 305.CrossRefPubMedGoogle Scholar
  92. Wen, P.H., Shao, X., Shao, Z., Hof, P.R., Wisniewski, T., Kelley, K., Friedrich, V.L., Jr., Ho, L., Pasinetti, G.M., Shioi, J., Robakis, N.K. and Elder, G.A., 2002, Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice. Neurobiol. Dis. 10: 8.CrossRefPubMedGoogle Scholar
  93. Yang, Y., Mufson, E.J. and Herrup, K., 2003, Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J. Neurosci. 23: 2557.PubMedGoogle Scholar
  94. Yoshimi, K., Ren, Y.R., Seki, T., Yamada, M., Ooizumi, H., Onodera, M., Saito, Y., Murayama, S., Okano, H., Mizuno, Y. and Mochizuki, H., 2005, Possibility for neurogenesis in substantia nigra of parkinsonian brain. Ann. Neurol. 58: 31.CrossRefPubMedGoogle Scholar
  95. Zarow, C., Vinters, H.V., Ellis, W.G., Weiner, M.W., Mungas, D., White, L. and Chui, H.C., 2005, Correlates of hippocampal neuron number in Alzheimer’s disease and ischemic vascular dementia. Ann. Neurol. 57: 896.CrossRefPubMedGoogle Scholar
  96. Zhao, M., Momma, S., Delfani, K., Carlen, M., Cassidy, R.M., Johansson, C.B., Brismar, H., Shupliakov, O., Frisen, J. and Janson, A.M., 2003, Evidence for neurogenesis in the adult mammalian substantia nigra. Proc. Natl Acad. Sci. USA 100: 7925.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Tomas Deierborg
    • 1
  • Jia- Yi Li
    • 1
  • Patrik Brundin
    • 1
  1. 1.Neuronal Survival Unit, Wallenberg Neuroscience Center, Dep. Experimental Medical SienceLund UniversitySweden

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