Cholinergic Neurodegeneration in Alzheimer's Disease: Basis for Nerve Growth Factor Therapy

  • Ahmad Salehi
  • Alexander Kleshevnikov
  • William C. Mobley

Neurotrophins play an important role in the survival, differentiation, and maintenance of neurons selectively involved in a number of disorders of the nervous system. Nerve growth factor (NGF) plays a vital role for basal forebrain cholinergic neurons (BFCNs), including the maintenance of the cholinergic phenotype in adults. Recognition of this role has suggested the use of NGF to ameliorate the loss of these neurons in Alzheimer’s disease (AD).


Nerve Growth Factor Down Syndrome Cholinergic Neuron Basal Forebrain Nucleus Basalis 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albeck, D. S., Backman, C., Veng, L., Friden, P., Rose, G. M., & Granholm, A. (1999). Acute application of NGF increases the firing rate of aged rat basal forebrain neurons. The European Journal of Neuroscience, 11, 2291–2304.CrossRefPubMedGoogle Scholar
  2. Alkondon, M., & Albuquerque, E. X. (2004). The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex. Progress in Brain Research, 145, 109–120.CrossRefPubMedGoogle Scholar
  3. Allen, S. J., Dawbarn, D., & Wilcock, G. K. (1988). Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer's disease. Brain Research, 454, 275–281.CrossRefPubMedGoogle Scholar
  4. Almaguer-Melian, W., Rosillo, J. C., Frey, J. U., & Bergado, J. A. (2006). Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats. Neuroscience, 138, 1083–1088.CrossRefPubMedGoogle Scholar
  5. Araujo, D. M., Lapchak, P. A., Collier, B., & Quirion, R. (1988). Characterization of N-[3H]methylcarbamylcholine binding sites and effect of N-methylcarbamylcholine on acetylcholine release in rat brain. Journal of Neurochemistry, 51, 292–299.CrossRefPubMedGoogle Scholar
  6. Arendt, T., Bigl, V., Arendt, A., & Tennstedt, A. (1983). Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease. Acta Neuropathologica, 61, 101–108.CrossRefPubMedGoogle Scholar
  7. Arendt, T., Bigl, V., & Arendt, A. (1984). Neurone loss in the nucleus basalis of Meynert in Creutzfeldt-Jakob disease. Acta Neuropathologica, 65, 85–88.CrossRefPubMedGoogle Scholar
  8. Arendt, T., Bigl, V., Tennstedt, A., & Arendt, A. (1985). Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience, 14, 1–14.CrossRefPubMedGoogle Scholar
  9. Arendt, T., Bruckner, M. K., Bigl, V., & Marcova, L. (1995). Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer's disease. II. Ageing, Korsakoff's disease, Parkinson's disease, and Alzheimer's disease. The Journal of Comparative Neurology, 351, 189–222.CrossRefPubMedGoogle Scholar
  10. Auerbach, J. M., & Segal, M. (1994). A novel cholinergic induction of long-term potentiation in rat hippocampus. Journal of Neurophysiology, 72, 2034–2040.PubMedGoogle Scholar
  11. Balse, E., Lazarus, C., Kelche, C., Jeltsch, H., Jackisch, R., & Cassel, J. C. (1999). Intrahippocampal grafts containing cholinergic and serotonergic fetal neurons ameliorate spatial reference but not working memory in rats with fimbria-fornix/cingular bundle lesions. Brain Research Bulletin, 49, 263–272.CrossRefPubMedGoogle Scholar
  12. Bartus, R. T., Dean, R. L., Goas, J. A., & Lippa, A. S. (1980). Age-related changes in passive avoidance retention: Modulation with dietary choline. Science, 209, 301–303.CrossRefPubMedGoogle Scholar
  13. Bartus, R. T., & Johnson, H. R. (1976). Short-term memory in the rhesus monkey: Disruption from the anti-cholinergic scopolamine. Pharmacology, Biochemistry, and Behavior, 5, 39–46.CrossRefPubMedGoogle Scholar
  14. Belichenko, P. V., Masliah, E., Kleschevnikov, A. M., Villar, A. J., Epstein, C. J., Salehi, A., et al. (2004). Synaptic structural abnormalities in the Ts65Dn mouse model of down syndrome. The Journal of Comparative Neurology, 480, 281–298.CrossRefPubMedGoogle Scholar
  15. Belichenko, P. V., Kleschevnikov, A. M., Salehi, A., Epstein, C. J., Mobley, C. W. (2007). Synaptic and cognitive abnormalities in mouse models of Down syndrome: Exploring genotype-phenotype relationship. Journal of Comparative Neurology, in press.Google Scholar
  16. Berger-Sweeney, J., Stearns, N. A., Murg, S. L., Floerke-Nashner, L. R., Lappi, D. A., & Baxter, M. G. (2001). Selective immunolesions of cholinergic neurons in mice: Effects on neuroanatomy, neurochemistry, and behavior. The Journal of Neuroscience, 21, 8164–8173.PubMedGoogle Scholar
  17. Bjorklund, A., Nilsson, O. G., & Kalen, P. (1990). Reafferentation of the subcortically denervated hippocampus as a model for transplant-induced functional recovery in the CNS. Progress in Brain Research, 83, 411–426.CrossRefPubMedGoogle Scholar
  18. Bland, B. H. (1986). The physiology and pharmacology of hippocampal formation theta rhythms. Progress in Neurobiology, 26, 1–54.CrossRefPubMedGoogle Scholar
  19. Bland, B. H. (2004). The power of theta: Providing insights into the role of the hippocampal formation in sensorimotor integration. Hippocampus, 14, 537–538.CrossRefPubMedGoogle Scholar
  20. Bland, B. H., & Colom, L. V. (1993). Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex. Progress in Neurobiology, 41, 157–208.CrossRefPubMedGoogle Scholar
  21. Bliss, T. V., & Collingridge, G. L. (1993). A synaptic model of memory: Long-term potentiation in the hippocampus. Nature, 361, 31–39.CrossRefPubMedGoogle Scholar
  22. Boissiere, F., Faucheux, B., Ruberg, M., Agid, Y., & Hirsch, E. C. (1997). Decreased TrkA gene expression in cholinergic neurons of the striatum and basal forebrain of patients with Alzheimer's disease. Experimental Neurology, 145, 245–252.CrossRefPubMedGoogle Scholar
  23. Boncristiano, S., Calhoun, M. E., Kelly, P. H., Pfeifer, M., Bondolfi, L., Stalder, M., et al. (2002). Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. The Journal of Neuroscience, 22, 3234–3243.PubMedGoogle Scholar
  24. Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., et al. (1997). Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron, 19, 939–945.CrossRefPubMedGoogle Scholar
  25. Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., et al. (1996). Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1–42/1–40 ratio in vitro and in vivo. Neuron, 17, 1005–1013.CrossRefPubMedGoogle Scholar
  26. Bowen, D. M., Smith, C. B., White, P., & Davison, A. N. (1976). Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain, 99, 459–496.CrossRefPubMedGoogle Scholar
  27. Bronfman, F. C., Moechars, D., & Van Leuven, F. (2000). Acetylcholinesterase-positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein london mutant transgenic mice. Neurobiology of Disease, 7, 152–168.CrossRefPubMedGoogle Scholar
  28. Brookmeyer, R., Gray, S., & Kawas, C. (1998). Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. American Journal of Public Health, 88, 1337–1342.CrossRefPubMedGoogle Scholar
  29. Brown, D. A., Abogadie, F. C., Allen, T. G., Buckley, N. J., Caulfield, M. P., Delmas, P., et al. (1997). Muscarinic mechanisms in nerve cells. Life Sciences, 60, 1137–1144.CrossRefPubMedGoogle Scholar
  30. Bruno, M. A., Clarke, P. B., Seltzer, A., Quirion, R., Burgess, K., Cuello, A. C., et al. (2004). Long-lasting rescue of age-associated deficits in cognition and the CNS cholinergic phenotype by a partial agonist peptidomimetic ligand of TrkA. The Journal of Neuroscience, 24, 8009–8018.CrossRefPubMedGoogle Scholar
  31. Burgard, E. C., & Sarvey, J. M. (1990). Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus. Neuroscience Letters, 116, 34–39.CrossRefPubMedGoogle Scholar
  32. Cabin, D. E., McKee-Johnson, J. W., Matesic, L. E., Wiltshire, T., Rue, E. E., Mjaatvedt, A. E., et al. (1998). Physical and comparative mapping of distal mouse chromosome 16. 5 p5. Genome Research, 8, 940–950.PubMedGoogle Scholar
  33. Caccamo, A., Oddo, S., Billings, L. M., Green, K. N., Martinez-Coria, H., Fisher, A., et al. M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron, 49, 671–682.Google Scholar
  34. Cao, X., & Sudhof, T. C. (2001). A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science, 293, 115–120.CrossRefPubMedGoogle Scholar
  35. Casaccia-Bonnefil, P., Carter, B. D., Dobrowsky, R. T., & Chao, M. V. (1996). Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature, 383, 716–719.CrossRefPubMedGoogle Scholar
  36. Cataldo, A. M., Petanceska, S., Peterhoff, C. M., Terio, N. B., Epstein, C. J., Villar, A., et al. App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. The Journal of Neuroscience, 23, 6788–6792.Google Scholar
  37. Cataldo, A. M., Petanceska, S., Terio, N. B., Peterhoff, C. M., Durham, R., Mercken, M., et al. (2004). Abeta localization in abnormal endosomes: Association with earliest Abeta elevations in AD and Down syndrome. Neurobiology of Aging, 25, 1263–1272.CrossRefPubMedGoogle Scholar
  38. Caulfield, M. P. (1993). Muscarinic receptors-Characterization, coupling and function. Pharmacology and Therapeutics, 58, 319–379.CrossRefPubMedGoogle Scholar
  39. Chen, C. P., Eastwood, S. L., Hope, T., McDonald, B., Francis, P. T., & Esiri, M. M. (2000). Immunocytochemical study of the dorsal and median raphe nuclei in patients with Alzheimer's disease prospectively assessed for behavioural changes. Neuropathology and Applied Neurobiology, 26, 347–355.CrossRefPubMedGoogle Scholar
  40. Chen, K. S., & Gage, F. H. (1995). Somatic gene transfer of NGF to the aged brain: Behavioral and morphological amelioration. The Journal of Neuroscience, 15, 2819–2825.PubMedGoogle Scholar
  41. Chen, K. S., Nishimura, M. C., Armanini, M. P., Crowley, C., Spencer, S. D., & Phillips, H. S. (1997). Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits. The Journal of Neuroscience, 17, 7288–7296.PubMedGoogle Scholar
  42. Chesselet, M. F. (1984). Presynaptic regulation of neurotransmitter release in the brain: Facts and hypothesis. Neuroscience, 12, 347–375.CrossRefPubMedGoogle Scholar
  43. Cobb, S. R., & Davies, C. H. (2005). Cholinergic modulation of hippocampal cells and circuits. The Journal of Physiology, 562, 81–88.CrossRefPubMedGoogle Scholar
  44. Cooper, J. D., Salehi, A., Delcroix, J. D., Howe, C. L., Belichenko, P. V., Chua-Couzens, J., et al. (2001). Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proceedings of the National Academy of Sciences of the United States of America, 98, 10439–10444.CrossRefPubMedGoogle Scholar
  45. Cooper, J. D., Skepper, J. N., Berzaghi, M. D., Lindholm, D., & Sofroniew, M. V. (1996). Delayed death of septal cholinergic neurons after excitotoxic ablation of hippocampal neurons during early postnatal development in the rat. Experimental Neurology, 139, 143–155.CrossRefPubMedGoogle Scholar
  46. da Cruz, M. T., Cardoso, A. L., de Almeida, L. P., Simoes, S., & de Lima, M. C. (2005). Tf-lipoplex-mediated NGF gene transfer to the CNS: Neuronal protection and recovery in an excitotoxic model of brain injury. Gene Therapy, 12, 1242–1252.CrossRefPubMedGoogle Scholar
  47. Davis, K. L., Mohs, R. C., Marin, D., Purohit, D. P., Perl, D. P., Lantz, M., et al. (1999). Cholinergic markers in elderly patients with early signs of Alzheimer disease. The Journal of the American Medical Association, 281, 1401–1406.CrossRefGoogle Scholar
  48. De Rosa, R., Garcia, A. A., Braschi, C., Capsoni, S., Maffei, L., Berardi, N., et al. (2005). Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 3811–3816.CrossRefPubMedGoogle Scholar
  49. de Sevilla, D. F., Cabezas, C., de Prada, A. N., Sanchez-Jimenez, A., & Buno, W. (2002). Selective muscarinic regulation of functional glutamatergic Schaffer collateral synapses in rat CA1 pyramidal neurons. The Journal of Physiology, 545, 51–63.CrossRefGoogle Scholar
  50. DeFreitas, M. F., McQuillen, P. S., & Shatz, C. J. (2001). A novel p75NTR signaling pathway promotes survival, not death, of immunopurified neocortical subplate neurons. The Journal of Neuroscience, 21, 5121–5129.PubMedGoogle Scholar
  51. Delcroix, J. D., Valletta, J. S., Wu, C., Hunt, S. J., Kowal, A. S., & Mobley, W. C. (2003). NGF signaling in sensory neurons: Evidence that early endosomes carry NGF retrograde signals. Neuron, 39, 69–84.CrossRefPubMedGoogle Scholar
  52. Denham, M. J., & Borisyuk, R. M. (2000). A model of theta rhythm production in the septal-hippocampal system and its modulation by ascending brain stem pathways. Hippocampus, 10, 698–716.CrossRefPubMedGoogle Scholar
  53. Diez, M., Danner, S., Frey, P., Sommer, B., Staufenbiel, M., Wiederhold, K. H., & Hokfelt, T. (2003). Neuropeptide alterations in the hippocampal formation and cortex of transgenic mice overexpressing beta-amyloid precursor protein (APP) with the Swedish double mutation (APP23). Neurobiology of Disease, 14, 579–594.CrossRefPubMedGoogle Scholar
  54. Divac, I. (1975). Magnocellular nuclei of the basal forebrain project to neocortex, brain stem, and olfactory bulb. Review of some functional correlates. Brain Research, 93, 385–398.Google Scholar
  55. Dobransky, T., & Rylett, R. J. (2005). A model for dynamic regulation of choline acetyltransferase by phosphorylation. Journal of Neurochemistry, 95, 305–313.CrossRefPubMedGoogle Scholar
  56. Douglas, C. L., Baghdoyan, H. A., & Lydic, R. (2001). M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse. The Journal of Pharmacology and Experimental Therapeutics, 299, 960–966.PubMedGoogle Scholar
  57. Drachman, D. A., & Leavitt, J. (1974). Human memory and the cholinergic system. A relationship to aging? Archives of Neurology, 30, 113–121.PubMedGoogle Scholar
  58. Drachman, D. A., & Sahakian, B. J. (1980). Memory and cognitive function in the elderly. A preliminary trial of physostigmine. Archives of Neurology, 37, 674–675.Google Scholar
  59. Dyrks, T., Monning, U., Beyreuther, K., & Turner, J. (1994). Amyloid precursor protein secretion and beta A4 amyloid generation are not mutually exclusive. FEBS Letters, 349, 210–214.CrossRefPubMedGoogle Scholar
  60. Edeline, J. M., Hars, B., Maho, C., & Hennevin, E. (1994). Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex. Experimental Brain Research, 97, 373–386.CrossRefGoogle Scholar
  61. Epstein, C. J. (2002). 2001 William Allan Award Address. From Down syndrome to the “human” in “human genetics”. American Journal of Human Genetics, 70, 300–313.CrossRefPubMedGoogle Scholar
  62. Escorihuela, R. M., Fernandez-Teruel, A., Vallina, I. F., Baamonde, C., Lumbreras, M. A., Dierssen, M., et al. (1995). A behavioral assessment of Ts65Dn mice: A putative Down syndrome model. Neuroscience Letters, 199, 143–146.CrossRefPubMedGoogle Scholar
  63. Escorihuela, R. M., Vallina, I. F., Martinez-Cue, C., Baamonde, C., Dierssen, M., Tobena, A., et al. (1998). Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome. Neuroscience Letters, 247, 171–174.CrossRefPubMedGoogle Scholar
  64. Etienne, P., Robitaille, Y., Gauthier, S., & Nair, N. P. (1986). Nucleus basalis neuronal loss and neuritic plaques in advanced Alzheimer's disease. Canadian Journal of Physiology and Pharmacology, 64, 318–324.PubMedGoogle Scholar
  65. Fahnestock, M., Scott, S. A., Jette, N., Weingartner, J. A., & Crutcher, K. A. (1996). Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer's disease parietal cortex. Brain Research, Molecular Brain Research, 42, 175–178.CrossRefGoogle Scholar
  66. Fantie, B. D., & Goddard, G. V. (1982). Septal modulation of the population spike in the fascia dentata produced by perforant path stimulation in the rat. Brain Research, 252, 227–237.CrossRefPubMedGoogle Scholar
  67. Finger, S. (1994). Origins of Neuroscience, New York: Oxford University Press.Google Scholar
  68. Freund, T. F., & Buzsaki, G. (1996). Interneurons of the hippocampus. Hippocampus, 6, 347–470.CrossRefPubMedGoogle Scholar
  69. Fujii, S., & Sumikawa, K. (2001). Nicotine accelerates reversal of long-term potentiation and enhances long-term depression in the rat hippocampal CA1 region. Brain Research, 894, 340–346.CrossRefPubMedGoogle Scholar
  70. Gabuzda, D., Busciglio, J., & Yankner, B. A. (1993). Inhibition of beta-amyloid production by activation of protein kinase C. Journal of Neurochemistry, 61, 2326–2329.CrossRefPubMedGoogle Scholar
  71. Gardiner, K., Fortna, A., Bechtel, L., & Davisson, M. T. (2003). Mouse models of Down syndrome: How useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions. Gene, 318, 137–147.CrossRefPubMedGoogle Scholar
  72. Ginsberg, S. D., Che, S., Counts, S. E., & Mufson, E. J. (2006). Single cell gene expression profiling in Alzheimer's disease. The Journal of the American Society for Experimental NeuroTherapeutics, 3, 302–318.Google Scholar
  73. Goedert, M., Fine, A., Dawbarn, D., Wilcock, G. K., & Chao, M. V. (1989). Nerve growth factor receptor mRNA distribution in human brain: Normal levels in basal forebrain in Alzheimer's disease. Brain Research Mol ecularBrain Research, 5, 1–7.CrossRefGoogle Scholar
  74. Gotti, C., Zoli, M., & Clementi, F. (2006). Brain nicotinic acetylcholine receptors: Native subtypes and their relevance. Trends in Pharmacological Sciences, 27, 482–491.CrossRefPubMedGoogle Scholar
  75. Granholm, A. C., Albeck, D., Backman, C., Curtis, M., Ebendal, T., Friden, P., et al. (1998). A non-invasive system for delivering neural growth factors across the blood-brain barrier: A review. Reviews in the Neurosciences, 9, 31–55.PubMedGoogle Scholar
  76. Gray, R., Rajan, A. S., Radcliffe, K. A., Yakehiro, M., & Dani, J. A. (1996). Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature, 383, 713–716.CrossRefPubMedGoogle Scholar
  77. Greig, N. H., Sambamurti, K., Yu, Q. S., Brossi, A., Bruinsma, G. B., & Lahiri, D. K. (2005). An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. Current Alzheimer Research, 2, 281–290.CrossRefPubMedGoogle Scholar
  78. Hamilton, S. E., & Nathanson, N. M. (2001). The M1 receptor is required for muscarinic activation of mitogen-activated protein (MAP) kinase in murine cerebral cortical neurons. The Journal of Biological Chemistry, 276, 15850–15853.CrossRefPubMedGoogle Scholar
  79. Hattori, M., Fujiyama, A., Taylor, T. D., Watanabe, H., Yada, T., Park, H. S., et al. (2000). The DNA sequence of human chromosome 21. Nature, 405, 311–319.CrossRefPubMedGoogle Scholar
  80. He, X. L., & Garcia, K. C. (2004). Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science, 304, 870–875.CrossRefPubMedGoogle Scholar
  81. Heimer, L., & Van Hoesen, G. W. (2006). The limbic lobe and its output channels: Implications for emotional functions and adaptive behavior. Neuroscience and Biobehavioral Reviews, 30, 126–147.CrossRefPubMedGoogle Scholar
  82. Higgins, G. A., Koh, S., Chen, K. S., & Gage, F. H. (1989). NGF induction of NGF receptor gene expression and cholinergic neuronal hypertrophy within the basal forebrain of the adult rat. Neuron, 3, 247–256.CrossRefPubMedGoogle Scholar
  83. Hodges, H., Allen, Y., Sinden, J., Lantos, P. L., & Gray, J. A. (1990). Cholinergic-rich transplants alleviate cognitive deficits in lesioned rats, but exacerbate response to cholinergic drugs. Progress in Brain Research, 82, 347–358.CrossRefPubMedGoogle Scholar
  84. Holtzman, D. M., Santucci, D., Kilbridge, J., Chua-Couzens, J., Fontana, D. J., Daniels, S. E., et al. (1996). Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proceedings of the National Academy of Sciences of the United States of America, 93, 13333–13338.CrossRefPubMedGoogle Scholar
  85. Hoogendijk, W. J., Pool, C. W., Troost, D., van Zwieten, E., & Swaab, D. F. (1995). Image analyser-assisted morphometry of the locus coeruleus in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Brain, 118(Pt. 1), 131–143.CrossRefPubMedGoogle Scholar
  86. Howe, C. L., & Mobley, W. C. (2005). Long-distance retrograde neurotrophic signaling. Current Opinion in Neurobiology, 15, 40–48.CrossRefPubMedGoogle Scholar
  87. Hu, L., Wong, T. P., Cote, S. L., Bell, K. F., and Cuello, A. C. (2003). The impact of Abeta-plaques on cortical cholinergic and non-cholinergic presynaptic boutons in alzheimer's disease-like transgenic mice. Neuroscience, 121, 421–432.CrossRefPubMedGoogle Scholar
  88. Huang, L. F., Cartwright, W. S., & Hu, T. W. (1988). The economic cost of senile dementia in the United States, 1985. Public Health Reports, 103, 3–7.PubMedGoogle Scholar
  89. Hudon, C., Dore, F. Y., & Goulet, S. (2002). Spatial memory and choice behavior in the radial arm maze after fornix transection. Progress in Neuro-psychopharmacology and Biological Psychiatry, 26, 1113–1123.CrossRefPubMedGoogle Scholar
  90. Huerta, P. T., & Lisman, J. E. (1993). Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature, 364, 723–725.CrossRefPubMedGoogle Scholar
  91. Hunter, B. E., de Fiebre, C. M., Papke, R. L., Kem, W. R., & Meyer, E. M. (1994). A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus. Neuroscience Letters, 168, 130–134.CrossRefPubMedGoogle Scholar
  92. Jaffar, S., Counts, S. E., Ma, S. Y., Dadko, E., Gordon, M. N., Morgan, D., et al. (2001). Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: Alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway. Experimental Neurology, 170, 227–243.CrossRefPubMedGoogle Scholar
  93. Jakab, R. L., & Leranth, C. (1995). Septum. In G. Paxinos (Ed.), The rat nervous system (pp. 405–442). San Diego: Academic Press.Google Scholar
  94. Jankowsky, J. L., Slunt, H. H., Gonzales, V., Jenkins, N. A., Copeland, N. G., & Borchelt, D. R. (2004). APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiology of Aging, 25, 885–892.CrossRefPubMedGoogle Scholar
  95. Jensen, A. A., Frolund, B., Liljefors, T., & Krogsgaard-Larsen, P. (2005). Neuronal nicotinic acetylcholine receptors: Structural revelations, target identifications, and therapeutic inspirations. Journal of Medicinal Chemistry, 48, 4705–4745.CrossRefPubMedGoogle Scholar
  96. Johnston, M. V., McKinney, M., & Coyle, J. T. (1979). Evidence for a cholinergic projection to neocortex from neurons in basal forebrain. Proceedings of the National Academy of Sciences of the United States of America, 76, 5392–5396.CrossRefPubMedGoogle Scholar
  97. Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., et al. (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325, 733–736.CrossRefPubMedGoogle Scholar
  98. Kar, S., Issa, A. M., Seto, D., Auld, D. S., Collier, B., & Quirion, R. (1998). Amyloid beta-peptide inhibits high-affinity choline uptake and acetylcholine release in rat hippocampal slices. Journal of Neurochemistry, 70, 2179–2187.PubMedGoogle Scholar
  99. Kar, S., Seto, D., Gaudreau, P., & Quirion, R. (1996). Beta-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal slices. The Journal of Neuroscience, 16, 1034–1040.PubMedGoogle Scholar
  100. Kar, S., Slowikowski, S. P., Westaway, D., & Mount, H. T. (2004). Interactions between beta-amyloid and central cholinergic neurons: Implications for Alzheimer's disease. Journal of Psychiatry and Neuroscience, 29, 427–441.PubMedGoogle Scholar
  101. Kilgard, M. P., & Merzenich, M. M. (1998). Cortical map reorganization enabled by nucleus basalis activity. Science, 279, 1714–1718.CrossRefPubMedGoogle Scholar
  102. Kirkwood, A., Rozas, C., Kirkwood, J., Perez, F., & Bear, M. F. (1999). Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. The Journal of Neuroscience, 19, 1599–1609.PubMedGoogle Scholar
  103. Kleschevnikov, A. M., Belichenko, P. V., Villar, A. J., Epstein, C. J., Malenka, R. C., & Mobley, W. C. (2004). Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. The Journal of Neuroscience, 24, 8153–8160.CrossRefPubMedGoogle Scholar
  104. Korsching, S., Auburger, G., Heumann, R., Scott, J., & Thoenen, H. (1985). Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. The EMBO Journal, 4, 1389–1393.PubMedGoogle Scholar
  105. Lamb, B. T., Sisodia, S. S., Lawler, A. M., Slunt, H. H., Kitt, C. A., Kearns, W. G., et al. (1993). Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nature Genetics, 5, 22–30.CrossRefPubMedGoogle Scholar
  106. Lamprea, M. R., Cardenas, F. P., Silveira, R., Morato, S., & Walsh, T. J. (2000). Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: Forebrain cholinergic mechanisms. Behavioural Brain Research, 117, 97–105.CrossRefPubMedGoogle Scholar
  107. Lanzafame, A. A., Christopoulos, A., & Mitchelson, F. (2003). Cellular signaling mechanisms for muscarinic acetylcholine receptors. Receptors Channels, 9, 241–260.CrossRefPubMedGoogle Scholar
  108. Larson, J., Wong, D., & Lynch, G. (1986). Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Research, 368, 347–350.CrossRefPubMedGoogle Scholar
  109. LeBlanc, A. C., Koutroumanis, M., & Goodyer, C. G. (1998). Protein kinase C activation increases release of secreted amyloid precursor protein without decreasing Abeta production in human primary neuron cultures. The Journal of Neuroscience, 18, 2907–2913.PubMedGoogle Scholar
  110. Lee, F. S., Rajagopal, R., Kim, A. H., Chang, P. C., & Chao, M. V. (2002). Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase-activating polypeptides. The Journal of Biological Chemistry, 277, 9096–9102.CrossRefPubMedGoogle Scholar
  111. Leranth, C., & Frotscher, M. (1987). Cholinergic innervation of hippocampal GAD- and somatostatin-immunoreactive commissural neurons. The Journal of Comparative Neurology, 261, 33–47.CrossRefPubMedGoogle Scholar
  112. Levey, A. I., Kitt, C. A., Simonds, W. F., Price, D. L., & Brann, M. R. (1991). Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. The Journal of Neuroscience, 11, 3218–3226.PubMedGoogle Scholar
  113. Levy, E., Carman, M. D., Fernandez-Madrid, I. J., Power, M. D., Lieberburg, I., van Duinen, S. G., et al. (1990). Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science, 248, 1124–1126.CrossRefPubMedGoogle Scholar
  114. Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., et al. (1995). Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science, 269, 973–977.CrossRefPubMedGoogle Scholar
  115. Lewin, G. R., Rueff, A., & Mendell, L. M. (1994). Peripheral and central mechanisms of NGF-induced hyperalgesia. The European Journal of Neuroscience, 6, 1903–1912.CrossRefPubMedGoogle Scholar
  116. Li, Y., Holtzman, D. M., Kromer, L. F., Kaplan, D. R., Chua-Couzens, J., Clary, D. O., et al. (1995). Regulation of TrkA and ChAT expression in developing rat basal forebrain: Evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons. The Journal of Neuroscience, 15, 2888–2905.PubMedGoogle Scholar
  117. Loeb, D. M., Maragos, J., Martin-Zanca, D., Chao, M. V., Parada, L. F., & Greene, L. A. (1991). The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines. Cell, 66, 961–966.CrossRefPubMedGoogle Scholar
  118. Loffelholz, K. (1996). Muscarinic receptors and cell signalling. Progress in Brain Research, 109, 191–194.CrossRefPubMedGoogle Scholar
  119. Longo, F. M., & Massa, S. M. (2005). Neurotrophin receptor-based strategies for Alzheimer's disease. Current Alzheimer Research, 2, 167–169.CrossRefPubMedGoogle Scholar
  120. Loy, R., Taglialatela, G., Angelucci, L., Heyer, D., & Perez-Polo, R. (1994). Regional CNS uptake of blood-borne nerve growth factor. Journal of Neuroscience Research, 39, 339–346.CrossRefPubMedGoogle Scholar
  121. Malenka, R. C., & Bear, M. F. (2004). LTP and LTD: An embarrassment of riches. Neuron, 44, 5–21.CrossRefPubMedGoogle Scholar
  122. Maliartchouk, S., Feng, Y., Ivanisevic, L., Debeir, T., Cuello, A. C., Burgess, K., et al. (2000). A designed peptidomimetic agonistic ligand of TrkA nerve growth factor receptors. Molecular Pharmacology, 57, 385–391.PubMedGoogle Scholar
  123. Mann, D. M., Yates, P. O., Marcyniuk, B., & Ravindra, C. R. (1985). Pathological evidence for neurotransmitter deficits in Down's syndrome of middle age. Journal of Mental Deficiency Research, 29(Pt. 2), 125–135.PubMedGoogle Scholar
  124. Marrosu, F., Portas, C., Mascia, M. S., Casu, M. A., Fa, M., Giagheddu, M., et al. (1995). Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats. Brain Research, 671, 329–332.CrossRefPubMedGoogle Scholar
  125. Massa, S. M., Xie, Y., Yang, T., Harrington, A. W., Kim, M. L., Yoon, S. O., et al. (2006). Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death. The Journal of Neuroscience, 26, 5288–5300.CrossRefPubMedGoogle Scholar
  126. Massey, P. V., Bhabra, G., Cho, K., Brown, M. W., & Bashir, Z. I. (2001). Activation of muscarinic receptors induces protein synthesis-dependent long-lasting depression in the perirhinal cortex. The European Journal of Neuroscience, 14, 145–152.CrossRefPubMedGoogle Scholar
  127. Matsuyama, S., Matsumoto, A., Enomoto, T., & Nishizaki, T. (2000). Activation of nicotinic acetylcholine receptors induces long-term potentiation in vivo in the intact mouse dentate gyrus. The European Journal of Neuroscience, 12, 3741–3747.CrossRefPubMedGoogle Scholar
  128. Maurer, K., Volk, S., & Gerbaldo, H. (1997). Auguste D and Alzheimer's disease. Lancet, 349, 1546–1549.CrossRefPubMedGoogle Scholar
  129. McCartney, H., Johnson, A. D., Weil, Z. M., & Givens, B. (2004). Theta reset produces optimal conditions for long-term potentiation. Hippocampus, 14, 684–687.CrossRefPubMedGoogle Scholar
  130. McCormick, D. A. (1989). Cholinergic and noradrenergic modulation of thalamocortical processing. Trends in Neurosciences, 12, 215–221.CrossRefPubMedGoogle Scholar
  131. Mesulam, M. M. (1990). Human brain cholinergic pathways. Progress in Brain Research, 84, 231–241.CrossRefPubMedGoogle Scholar
  132. Mesulam, M. M. (1995). Cholinergic pathways and the ascending reticular activating system of the human brain. Annals of the New York Academy of Sciences, 757, 169–179.CrossRefPubMedGoogle Scholar
  133. Mesulam, M. M. (1996). The systems-level organization of cholinergic innervation in the human cerebral cortex and its alterations in Alzheimer's disease. Progress in Brain Research, 109, 285–297.CrossRefPubMedGoogle Scholar
  134. Mesulam, M. M., Mufson, E. J., Levey, A. I., & Wainer, B. H. (1983). Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. The Journal of Comparative Neurology, 214, 170–197.CrossRefPubMedGoogle Scholar
  135. Mesulam, M. M., Mufson, E. J., Levey, A. I., & Wainer, B. H. (1984). Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Neuroscience, 12, 669–686.CrossRefPubMedGoogle Scholar
  136. Mesulam, M. M., Mufson, E. J., Wainer, B. H., & Levey, A. I. (1983). Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6). Neuroscience, 10, 1185–1201.CrossRefPubMedGoogle Scholar
  137. Mesulam, M. M., Rosen, A. D., & Mufson, E. J. (1984). Regional variations in cortical cholinergic innervation: Chemoarchitectonics of acetylcholinesterase-containing fibers in the macaque brain. Brain Research, 311, 245–258.CrossRefPubMedGoogle Scholar
  138. Mesulam, M., Shaw, P., Mash, D., & Weintraub, S. (2004). Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Annals of Neurology, 55, 815–828.CrossRefPubMedGoogle Scholar
  139. Mesulam, M. M., & Van Hoesen, G. W. (1976). Acetylcholinesterase-rich projections from the basal forebrain of the rhesus monkey to neocortex. Brain Research, 109, 152–157.CrossRefPubMedGoogle Scholar
  140. Mobley, W. C., Rutkowski, J. L., Tennekoon, G. I., Buchanan, K., & Johnston, M. V. (1985). Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science, 229, 284–287.CrossRefPubMedGoogle Scholar
  141. Mufson, E. J., Conner, J. M., & Kordower, J. H. (1995). Nerve growth factor in Alzheimer's disease: Defective retrograde transport to nucleus basalis. Neuroreport, 6, 1063–1066.CrossRefPubMedGoogle Scholar
  142. Mufson, E. J., Kroin, J. S., Sendera, T. J., & Sobreviela, T. (1999). Distribution and retrograde transport of trophic factors in the central nervous system: Functional implications for the treatment of neurodegenerative diseases. Progress in Neurobiology, 57, 451–484.CrossRefPubMedGoogle Scholar
  143. Mufson, E. J., Lavine, N., Jaffar, S., Kordower, J. H., Quirion, R., & Saragovi, H. U. (1997). Reduction in p140-TrkA receptor protein within the nucleus basalis and cortex in Alzheimer's disease. Experimental Neurology, 146, 91–103.CrossRefPubMedGoogle Scholar
  144. Mufson, E. J., Ma, S. Y., Dills, J., Cochran, E. J., Leurgans, S., Wuu, J., et al. (2002). Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease. The Journal of Comparative Neurology, 443, 136–153.CrossRefPubMedGoogle Scholar
  145. Nilsson, L., Nordberg, A., Hardy, J., Wester, P., & Winblad, B. (1986). Physostigmine restores 3H-acetylcholine efflux from Alzheimer brain slices to normal level. Journal of Neural Transmission, 67, 275–285.CrossRefPubMedGoogle Scholar
  146. Nitsch, R. M., Slack, B. E., Wurtman, R. J., & Growdon, J. H. (1992). Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science, 258, 304–307.CrossRefPubMedGoogle Scholar
  147. Nonomura, T., Nishio, C., Lindsay, R. M., & Hatanaka, H. (1995). Cultured basal forebrain cholinergic neurons from postnatal rats show both overlapping and non-overlapping responses to the neurotrophins. Brain Research, 683, 129–139.CrossRefPubMedGoogle Scholar
  148. Olton, D. S. (1977). The function of septo-hippocampal connections in spatially organized behaviour. Ciba Foundation Symposium, 327–349.Google Scholar
  149. Orr, G., Rao, G., Houston, F. P., McNaughton, B. L., & Barnes, C. A. (2001). Hippocampal synaptic plasticity is modulated by theta rhythm in the fascia dentata of adult and aged freely behaving rats. Hippocampus, 11, 647–654.CrossRefPubMedGoogle Scholar
  150. Ovsepian, S. V. (2006). Enhancement of the synchronized firing of CA1 pyramidal cells by medial septum preconditioning: Time-dependent involvement of muscarinic cholinoceptors and GABAB receptors. Neuroscience Letters, 393, 1–6.CrossRefPubMedGoogle Scholar
  151. Ovsepian, S. V., Anwyl, R., & Rowan, M. J. (2004). Endogenous acetylcholine lowers the threshold for long-term potentiation induction in the CA1 area through muscarinic receptor activation: In vivo study. The European Journal of Neuroscience, 20, 1267–1275.CrossRefPubMedGoogle Scholar
  152. Paterson, D., & Nordberg, A. (2000). Neuronal nicotinic receptors in the human brain. Progress in Neurobiology, 61, 75–111.CrossRefPubMedGoogle Scholar
  153. Pearson, R. C., Sofroniew, M. V., Cuello, A. C., Powell, T. P., Eckenstein, F., Esiri, M. M., et al. (1983). Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer's type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Research, 289, 375–379.CrossRefPubMedGoogle Scholar
  154. Pehar, M., Cassina, P, M., V., Xie, Y., Beckman, J. S., Massa, S. M., Longo, F. M., et al. (2006). Modulation of p75NTR-dependent motor neuron death by a small non-peptidyl mimetic of the neurotrophin loop 1 domain. The European Journal of Neuroscience, In press.Google Scholar
  155. Perry, E. K., Morris, C. M., Court, J. A., Cheng, A., Fairbairn, A. F., McKeith, I. G., et al. (1995). Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: Possible index of early neuropathology. Neuroscience, 64, 385–395.CrossRefPubMedGoogle Scholar
  156. Perry, T., Hodges, H., & Gray, J. A. (2001). Behavioural, histological and immunocytochemical consequences following 192 IgG-saporin immunolesions of the basal forebrain cholinergic system. Brain Research Bulletin, 54, 29–48.CrossRefPubMedGoogle Scholar
  157. Pitler, T. A., & Alger, B. E. (1992). Cholinergic excitation of GABAergic interneurons in the rat hippocampal slice. The Journal of Physiology, 450, 127–142.PubMedGoogle Scholar
  158. Pittel, Z., Heldman, E., Rubinstein, R., & Cohen, S. (1990). Distinct muscarinic receptor subtypes differentially modulate acetylcholine release from corticocerebral synaptosomes. Journal of Neurochemistry, 55, 665–672.CrossRefPubMedGoogle Scholar
  159. Prado, M. A., Reis, R. A., Prado, V. F., de Mello, M. C., Gomez, M. V., & de Mello, F. G. (2002). Regulation of acetylcholine synthesis and storage. Neurochemistry International, 41, 291–299.CrossRefPubMedGoogle Scholar
  160. Procter, A. W., Lowe, S. L., Palmer, A. M., Francis, P. T., Esiri, M. M., Stratmann, G. C., et al. Topographical distribution of neurochemical changes in Alzheimer's disease. Journal of the Neurological Sciences, 84, 125–140.Google Scholar
  161. Radcliffe, K. A., Fisher, J. L., Gray, R., & Dani, J. A. (1999). Nicotinic modulation of glutamate and GABA synaptic transmission of hippocampal neurons. Annals of the New York Academy of Sciences, 868, 591–610.CrossRefPubMedGoogle Scholar
  162. Rajagopal, R., & Chao, M. V. (2006). A role for Fyn in Trk receptor transactivation by G-protein-coupled receptor signaling. Molecular and Cellular Neurosciences, 33, 34–46.Google Scholar
  163. Rinne, J. O., Paljarvi, L., & Rinne, U. K. (1987). Neuronal size and density in the nucleus basalis of Meynert in Alzheimer's disease. Journal of the Neurological Sciences, 79, 67–76.CrossRefPubMedGoogle Scholar
  164. Roberson, M. R., & Harrell, L. E. (1997). Cholinergic activity and amyloid precursor protein metabolism. Brain Research Reviews, 25, 50–69.CrossRefPubMedGoogle Scholar
  165. Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., et al. (1995). Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature, 376, 775–778.CrossRefPubMedGoogle Scholar
  166. Roux, P. P., & Barker, P. A. (2002). Neurotrophin signaling through the p75 neurotrophin receptor. Progress in Neurobiology, 67, 203–233.CrossRefPubMedGoogle Scholar
  167. Ruberg, M., Mayo, W., Brice, A., Duyckaerts, C., Hauw, J. J., Simon, H., et al. (1990). Choline acetyltransferase activity and [3H]vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions. Neuroscience, 35, 327–333.CrossRefPubMedGoogle Scholar
  168. Ruberti, F., Capsoni, S., Comparini, A., Di Daniel, E., Franzot, J., Gonfloni, S., et al. (2000). Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy. The Journal of Neuroscience, 20, 2589–2601.PubMedGoogle Scholar
  169. Rylett, R. J., Ball, M. J., & Colhoun, E. H. (1983). Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease. Brain Research, 289, 169–175.CrossRefPubMedGoogle Scholar
  170. Sago, H., Carlson, E. J., Smith, D. J., Kilbridge, J., Rubin, E. M., Mobley, W. C., et al. (1998). Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proceedings of the National Academy of Sciences of the United States of America, 95, 6256–6261.CrossRefPubMedGoogle Scholar
  171. Salehi, A., Delcroix, J. D., & Mobley, W. C. (2003). Traffic at the intersection of neurotrophic factor signaling and neurodegeneration. Trends in Neurosciences, 26, 73–80.CrossRefPubMedGoogle Scholar
  172. Salehi, A., Delcroix, J. D., & Swaab, D. F. (2004). Alzheimer's disease and NGF signaling. Journal of Neural Transmission, 111, 323–345.CrossRefPubMedGoogle Scholar
  173. Salehi, A., Delcroix, J. D., Belichenko, P. V., Zhan, K., Wu, C., Valletta, J. S., 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.CrossRefPubMedGoogle Scholar
  174. Salehi, A., Lucassen, P. J., Pool, C. W., Gonatas, N. K., Ravid, R., & Swaab, D. F. (1994). Decreased neuronal activity in the nucleus basalis of Meynert in Alzheimer's disease as suggested by the size of the Golgi apparatus. Neuroscience, 59, 871–880.CrossRefPubMedGoogle Scholar
  175. Salehi, A., Ocampo, M., Verhaagen, J., & Swaab, D. F. (2000). P75 neurotrophin receptor in the nucleus basalis of Meynert in relation to age, sex, and Alzheimer's disease. Experimental Neurology, 161, 245–258.CrossRefPubMedGoogle Scholar
  176. Salehi, A., Verhaagen, J., Dijkhuizen, P. A., & Swaab, D. F. (1996). Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease. Neuroscience, 75, 373–387.CrossRefPubMedGoogle Scholar
  177. Samuel, W., Terry, R. D., DeTeresa, R., Butters, N., & Masliah, E. (1994). Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Archives of Neurology, 51, 772–778.PubMedGoogle Scholar
  178. Sankaranarayanan, S. (2006). Genetically modified mice models for Alzheimer's disease. Current Topics in Medicinal Chemistry, 6, 609–627.CrossRefPubMedGoogle Scholar
  179. Sarter, M., & Bruno, J. P. (1997). Cognitive functions of cortical acetylcholine: Toward a unifying hypothesis. Brain Research Reviews, 23, 28–46.CrossRefPubMedGoogle Scholar
  180. Sassin, I., Schultz, C., Thal, D. R., Rub, U., Arai, K., Braak, E., et al. (2000). Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathologica, 100, 259–269.CrossRefPubMedGoogle Scholar
  181. Scott, S. A., Mufson, E. J., Weingartner, J. A., Skau, K. A., & Crutcher, K. A. (1995). Nerve growth factor in Alzheimer's disease: Increased levels throughout the brain coupled with declines in nucleus basalis. The Journal of Neuroscience, 15, 6213–6221.PubMedGoogle Scholar
  182. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., et al. (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature, 375, 754–760.CrossRefPubMedGoogle Scholar
  183. Shinoe, T., Matsui, M., Taketo, M. M., & Manabe, T. (2005). Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus. The Journal of Neuroscience, 25, 11194–11200.CrossRefPubMedGoogle Scholar
  184. Shivers, B. D., Hilbich, C., Multhaup, G., Salbaum, M., Beyreuther, K., & Seeburg, P. H. (1988). Alzheimer's disease amyloidogenic glycoprotein: Expression pattern in rat brain suggests a role in cell contact. The EMBO Journal, 7, 1365–1370.PubMedGoogle Scholar
  185. Sofroniew, M. V., Cooper, J. D., Svendsen, C. N., Crossman, P., Ip, N. Y., Lindsay, R. M., et al. (1993). Atrophy but not death of adult septal cholinergic neurons after ablation of target capacity to produce mRNAs for NGF, BDNF, and NT3. The Journal of Neuroscience, 13, 5263–5276.PubMedGoogle Scholar
  186. Sofroniew, M. V., Howe, C. L., & Mobley, W. C. (2001). Nerve growth factor signaling, neuroprotection, and neural repair. Annual Review of Neuroscience, 24, 1217–1281.CrossRefPubMedGoogle Scholar
  187. Sokolov, M. V., & Kleschevnikov, A. M. (1995). Atropine suppresses associative LTP in the CA1 region of rat hippocampal slices. Brain Research, 672, 281–284.CrossRefPubMedGoogle Scholar
  188. Stokin, G. B., Lillo, C., Falzone, T. L., Brusch, R. G., Rockenstein, E., Mount, S. L., et al. (2005). Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science, 307, 1282–1288.CrossRefPubMedGoogle Scholar
  189. Svendsen, C. N., Kew, J. N., Staley, K., & Sofroniew, M. V. (1994). Death of developing septal cholinergic neurons following NGF withdrawal in vitro: Protection by protein synthesis inhibition. The Journal of Neuroscience, 14, 75–87.PubMedGoogle Scholar
  190. Teipel, S. J., Flatz, W. H., Heinsen, H., Bokde, A. L., Schoenberg, S. O., Stockel, S., et al. (2005). Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain, 128, 2626–2644.CrossRefPubMedGoogle Scholar
  191. Toledano, A., & Alvarez, M. I. (2004). Lesions and dysfunctions of the nucleus basalis as Alzheimer's disease models: General and critical overview and analysis of the long-term changes in several excitotoxic models. Current Alzheimer Research, 1, 189–214.CrossRefPubMedGoogle Scholar
  192. Tuszynski, M. H., Thal, L., Pay, M., Salmon, D. P., U, H. S., Bakay, R., et al. (2005). A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nature Medicine, 11, 551–555.CrossRefPubMedGoogle Scholar
  193. Umbriaco, D., Garcia, S., Beaulieu, C., & Descarries, L. (1995). Relational features of acetylcholine, noradrenaline, serotonin and GABA axon terminals in the stratum radiatum of adult rat hippocampus (CA1). Hippocampus, 5, 605–620.CrossRefPubMedGoogle Scholar
  194. Utsugisawa, K., Nagane, Y., Obara, D., & Tohgi, H. (2002). Over-expression of alpha7 nicotinic acetylcholine receptor induces sustained ERK phosphorylation and N-cadherin expression in PC12 cells. Molecular Brain Research, 106, 88–93.CrossRefPubMedGoogle Scholar
  195. Utsuki, T., Yu, Q. S., Davidson, D., Chen, D., Holloway, H. W., Brossi, A., et al. (2006). Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptide. The Journal of Pharmacology and Experimental Therapeutics, 318, 855–862.CrossRefPubMedGoogle Scholar
  196. Valentino, R. J., & Dingledine, R. (1981). Presynaptic inhibitory effect of acetylcholine in the hippocampus. The Journal of Neuroscience, 1, 784–792.PubMedGoogle Scholar
  197. Vannucchi, M. G., & Pepeu, G. (1995). Muscarinic receptor modulation of acetylcholine release from rat cerebral cortex and hippocampus. Neuroscience Letters, 190, 53–56.CrossRefPubMedGoogle Scholar
  198. Vas, C., Rajkumar, S., Tanyakitpisal, P., & Chandra, V. (2001). When old age becomes a disease. WHO, Regional Office for South-East Asia.
  199. Vertes, R. P., & Kocsis, B. (1997). Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience, 81, 893–926.CrossRefPubMedGoogle Scholar
  200. Vinogradova, O. S. (1995). Expression, control, and probable functional significance of the neuronal theta-rhythm. Progress in Neurobiology, 45, 523–583.CrossRefPubMedGoogle Scholar
  201. Vizi, E. S., & Kiss, J. P. (1998). Neurochemistry and pharmacology of the major hippocampal transmitter systems: Synaptic and nonsynaptic interactions. Hippocampus, 8, 566–607.CrossRefPubMedGoogle Scholar
  202. Vizi, E. S., Kobayashi, O., Torocsik, A., Kinjo, M., Nagashima, H., Manabe, N., et al. (1989). Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release. Neuroscience, 31, 259–267.CrossRefPubMedGoogle Scholar
  203. Vizi, E. S., Ono, K., Adam-Vizi, V., Duncalf, D., & Foldes, F. F. (1984). Presynaptic inhibitory effect of Met-enkephalin on [14C] acetylcholine release from the myenteric plexus and its interaction with muscarinic negative feedback inhibition. The Journal of Pharmacology and Experimental Therapeutics, 230, 493–499.PubMedGoogle Scholar
  204. Walsh, T. J., Herzog, C. D., Gandhi, C., Stackman, R. W., & Wiley, R. G. (1996). Injection of IgG 192-saporin into the medial septum produces cholinergic hypofunction and dose-dependent working memory deficits. Brain Research, 726, 69–79.CrossRefPubMedGoogle Scholar
  205. Wei, J., Walton, E. A., Milici, A., & Buccafusco, J. J. (1994). m1–m5 muscarinic receptor distribution in rat CNS by RT-PCR and HPLC. Journal of Neurochemistry, 63, 815–821.PubMedCrossRefGoogle Scholar
  206. Wenk, G. L. (1997). The nucleus basalis magnocellularis cholinergic system: One hundred years of progress. Neurobiology of Learning and Memory, 67, 85–95.CrossRefPubMedGoogle Scholar
  207. Wessendorf, M. W. (1991). Fluoro-Gold: Composition, and mechanism of uptake. Brain Research, 553, 135–148.CrossRefPubMedGoogle Scholar
  208. White, A. R., Reyes, R., Mercer, J. F., Camakaris, J., Zheng, H., Bush, A. I., et al. (1999). Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Research, 842, 439–444.CrossRefPubMedGoogle Scholar
  209. Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981). Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Annals of Neurology, 10, 122–126.CrossRefPubMedGoogle Scholar
  210. Wilkie, G. I., Hutson, P., Sullivan, J. P., & Wonnacott, S. (1996). Pharmacological characterization of a nicotinic autoreceptor in rat hippocampal synaptosomes. Neurochemical Research, 21, 1141–1148.CrossRefPubMedGoogle Scholar
  211. Winblad, B., Giacobini, E., Froelich, E., Bruinsma, G., Walters, E., & Friedhoff, L. (2006). Double-blind, placebo-controlled evaluation of the safety and efficacy of phenserine tartrate (pt) for the treatment of mild to moderate Alzheimer's disease (AD). Paper presented at the 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, Geneva.Google Scholar
  212. Winkler, J., Ramirez, G. A., Kuhn, H. G., Peterson, D. A., Day-Lollini, P. A., Stewart, G. R., et al. (1997). Reversible Schwann cell hyperplasia and sprouting of sensory and sympathetic neurites after intraventricular administration of nerve growth factor. Annals of Neurology, 41, 82–93.CrossRefPubMedGoogle Scholar
  213. Winters, B. D., & Dunnett, S. B. (2004). Selective lesioning of the cholinergic septo-hippocampal pathway does not disrupt spatial short-term memory: A comparison with the effects of fimbria-fornix lesions. Behavioral Neuroscience, 118, 546–562.CrossRefPubMedGoogle Scholar
  214. Wisniewski, K. E., Dalton, A. J., McLachlan, C., Wen, G. Y., & Wisniewski, H. M. (1985). Alzheimer's disease in Down's syndrome: Clinicopathologic studies. Neurology, 35, 957–961.PubMedGoogle Scholar
  215. Wolf, B. A., Wertkin, A. M., Jolly, Y. C., Yasuda, R. P., Wolfe, B. B., Konrad, R. J., et al. (1995). Muscarinic regulation of Alzheimer's disease amyloid precursor protein secretion and amyloid beta-protein production in human neuronal NT2N cells. The Journal of Biological Chemistry, 270, 4916–4922.CrossRefPubMedGoogle Scholar
  216. Wong, T. P., Debeir, T., Duff, K., & Cuello, A. C. (1999). Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. The Journal of Neuroscience, 19, 2706–2716.PubMedGoogle Scholar
  217. Wonnacott, S. (1997). Presynaptic nicotinic ACh receptors. Trends in Neurosciences, 20, 92–98.CrossRefPubMedGoogle Scholar
  218. Xie, Y., Ye, L., Zhang, X., Cui, W., Lou, J., Nagai, T., et al. (2005). Transport of nerve growth factor encapsulated into liposomes across the blood-brain barrier: In vitro and in vivo studies. Journal of Controlled Release, 105, 106–119.CrossRefPubMedGoogle Scholar
  219. Yoder, R. M., & Pang, K. C. (2005). Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm. Hippocampus, 15, 381–392.CrossRefPubMedGoogle Scholar
  220. Zaborszky, L., Pang, K., Somogyi, J., Nadasdy, Z., & Kallo, I. (1999). The basal forebrain corticopetal system revisited. Annals of the New York Academy of Sciences, 877, 339–367.CrossRefPubMedGoogle Scholar
  221. Zaccaro, M. C., Lee, H. B., Pattarawarapan, M., Xia, Z., Caron, A., L'Heureux, P. J., et al. (2005). Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities. Chemistry and Biology, 12, 1015–1028.CrossRefPubMedGoogle Scholar
  222. Zheng, W. H., Bastianetto, S., Mennicken, F., Ma, W., & Kar, S. (2002). Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. Neuroscience, 115, 201–211.CrossRefPubMedGoogle Scholar
  223. Zheng, H., Jiang, M., Trumbauer, M. E., Hopkins, R., Sirinathsinghji, D. J., Stevens, K. A., et al. (1996). Mice deficient for the amyloid precursor protein gene. Annals of the New York Academy of Sciences, 777, 421–426.CrossRefPubMedGoogle Scholar
  224. Zhou, J., Valletta, J. S., Grimes, M. L., & Mobley, W. C. (1995). Multiple levels for regulation of TrkA in PC12 cells by nerve growth factor. Journal of Neurochemistry, 65, 1146–1156.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ahmad Salehi
    • 1
  • Alexander Kleshevnikov
    • 1
  • William C. Mobley
    • 1
  1. 1.Department of Neurology and Neurological Sciences Neuroscience InstituteStanford UniversityStanfordUSA

Personalised recommendations