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Amyloid β-Peptide and Central Cholinergic Neurons: Involvement in Normal Brain Function and Alzheimer’s Disease Pathology

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Abeta Peptide and Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD), the most common form of dementia affecting individuals over 65 years of age, is a progressive neurodegenerative disorder. It is characterized by a global deterioration of intellectual function that includes an amnesic type of memory impairment, deterioration of language, and visuospatial deficits. Motor and sensory abnormalities are uncommon until the late phases of the disease, and basic activities of daily living are gradually impaired as the disease enters advanced phases. Psychosis and agitation also develop during middle or later phases of the disease. The average course of AD from the onset of clinical symptoms to death is approximately a decade, but the rate of progression is variable [1],[2]. Epidemiological data have shown that AD afflicts about 8–10% of the population over 65 years of age, and its prevalence doubles every 5 years thereafter [3].

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References

  1. Whitehouse PJ. Genesis of Alzheimer’s disease. Neurology 1997;48(Suppl 7):S2–7.

    CAS  Google Scholar 

  2. Katzman R. The prevalence and malignancy of Alzheimer’s disease. Arch Neurol 1976;33:217–8.

    PubMed  CAS  Google Scholar 

  3. Cummings JL. Alzheimer’s disease. N Engl J Med 2004;351:56–67.

    PubMed  CAS  Google Scholar 

  4. Holmes C. Genotype and phenotype in Alzheimer’s disease. Br J Psychiatry 2002;180:131–4.

    PubMed  Google Scholar 

  5. Bertram L, Tanzi RE. The current status of Alzheimer’s disease genetics: what do we tell patients? Pharmacol Res 2004;50:385–396.

    PubMed  CAS  Google Scholar 

  6. St George-Hyslop PH, Petit A. Molecular biology and genetics of Alzheimer’s disease. C R Biologies 2004;328:119–130.

    Google Scholar 

  7. Strittmatter WJ, Saunders AM, Schmeckel D, et al. Apolipoprotein E: High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer’s disease. Proc Natl Acad Sci USA 1993;90:1977–81.

    PubMed  CAS  Google Scholar 

  8. Poirier J, Davingnon J, Bouthillier D, et al. Apolipoprotein E polymorphism and Alzheimer’s disease. Lancet 1993;342:697–9.

    PubMed  CAS  Google Scholar 

  9. Selkoe DJ. Alzheimer’s disease: genes, proteins and therapy. Physiol Rev 2001;81:741–66.

    PubMed  CAS  Google Scholar 

  10. Muller-Spahn F, Hock C. Risk factors and differential diagnosis of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1999;249(Suppl 3):III/37–III/42.

    Google Scholar 

  11. Price DL, Sisodia SS. Mutant genes in familial Alzheimer’s disease and transgenic models. Annu Rev Neurosci 1998;21:479–505.

    PubMed  CAS  Google Scholar 

  12. Lee VM. Disruption of the cytoskeleton in Alzheimer’s disease. Curr Opin Neurobiol 1995;5:663–8.

    PubMed  CAS  Google Scholar 

  13. Iqbal K, Alonso Adel C, Chen S, et al. Tau pathology in Alzheimer’s disease and other tauopathies. Biochim Biophys Acta 2005;1739(2–3):198–210.

    PubMed  CAS  Google Scholar 

  14. Brion JP, Anderton BH, Authelet M, et al. Neurofibrillary tangles and tau phosphorylation. Biochem Soc Symp 2001;67:81–8.

    PubMed  CAS  Google Scholar 

  15. Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J 1997;323:577–91.

    PubMed  CAS  Google Scholar 

  16. Bierer LM, Hof PR, Purohit DP, et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease. Arch Neurol 1995;52:81–8.

    PubMed  CAS  Google Scholar 

  17. Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol 1997;56:321–39.

    PubMed  CAS  Google Scholar 

  18. Clippingdale AB, Wade JD, Barrow CJ. The amyloid-β peptide and its role in Alzheimer’s disease. J Peptide Sci 2001;7:227–49.

    CAS  Google Scholar 

  19. Wisniewski T, Ghiso J, Frangione B. Biology of Aβ amyloid in Alzheimer’s disease. Neurobiol Dis 1997; 4:313–28.

    PubMed  CAS  Google Scholar 

  20. Naslund J, Haroutunian V, Mohs R, et al. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 2000;283: 1571–7.

    PubMed  CAS  Google Scholar 

  21. McLean CA, Cherny RA, Fraser FW, et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 1999;46:860–6.

    PubMed  CAS  Google Scholar 

  22. Lue LF, Kuo YM, Roher AE, et al. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol 1999; 155:853–62.

    PubMed  CAS  Google Scholar 

  23. Tanzi RE. Neuropathology in the Down’s syndrome brain. Nat Med 1996;2:31–2.

    PubMed  CAS  Google Scholar 

  24. Pike CJ, Burdick D, Walencewicz AJ, et al. Neurodegeneration induced by β-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci 1993;13:1676–87.

    PubMed  CAS  Google Scholar 

  25. Yankner BA. Mechanisms of neuronal degeneration in Alzheimer’s disease. Neuron 1996;16:921–32.

    PubMed  CAS  Google Scholar 

  26. Games D, Adams D, Alessandrini R, et al. Alzheimer’s type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 1995;373:523–7.

    PubMed  CAS  Google Scholar 

  27. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 1996;274:99–102.

    PubMed  CAS  Google Scholar 

  28. Calhoun M, Wiederhold K, Abramowski D, et al. Neuron loss in APP transgenic mice. Nature 1998;395:755–6.

    PubMed  CAS  Google Scholar 

  29. Bondolfi L, Calhoun M, Ermini F, et al. Amyloidassociated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J Neurosci 2002;22:515–22.

    PubMed  CAS  Google Scholar 

  30. Giovannelli L, Casamenti F, Scali C, et al. Differential effects of amyloid peptides β-(1–40) and β-(25–35) injections into rat nucleus basalis. Neuroscience 1995;66:781–92.

    PubMed  CAS  Google Scholar 

  31. Harkany T, Abraham I, Timmerman W, et al. β-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis. Eur J Neurosci 2000;12:2735–45.

    PubMed  CAS  Google Scholar 

  32. Itoh A, Nitta A, Nadai M, et al. Dysfunction of cholinergic and dopaminergic neuronal systems in β-amyloid protein-infused rats. J Neurochem 1996;66: 1113–7.

    Article  PubMed  CAS  Google Scholar 

  33. Geula C, Wu CK, Saroff D, et al. Aging renders the brain vulnerable to amyloid β-protein neurotoxicity. Nat Med 1998;4:827–31.

    PubMed  CAS  Google Scholar 

  34. Gotz J, Chen F, van Dorpe J, et al. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001;293:1491–5.

    PubMed  CAS  Google Scholar 

  35. Lewis J, Dickson DW, Lin WL, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001;293:1487–91.

    PubMed  CAS  Google Scholar 

  36. Geula C, Mesulam MM. Cholinergic system and related neuropathological predilection patterns in Alzheimer’s disease. In: Terry RD, Katzman R, Bick KL, editors. Alzheimer’s Disease. New York: Raven Press Ltd.; 1994:263–91.

    Google Scholar 

  37. DeKosky ST, Scheff SW, Styren SD. Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 1996;5:417–21.

    PubMed  CAS  Google Scholar 

  38. Lander CJ, Lee JM. Pharmacological drug treatment of Alzheimer’s disease: the cholinergic hypothesis revisited. J Neuropathol Exp Neurol 1998;57:719–31.

    Google Scholar 

  39. Francis PT, Palmer AM, Snape M, et al. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 1999;66: 137–47.

    PubMed  CAS  Google Scholar 

  40. Davies P, Maloney AJF. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976;2:1403.

    PubMed  CAS  Google Scholar 

  41. Blusztajn JK, Berse B. The cholinergic neuronal phenotype in Alzheimer’s disease. Metab Brain Dis 2000;15:45–64.

    PubMed  CAS  Google Scholar 

  42. Perry EK, Tomlinson BE, Blessed G, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978;2:1457–9.

    Article  PubMed  CAS  Google Scholar 

  43. Bartus RT, Dean RLIII, Beer B, et al. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217:408–17.

    PubMed  CAS  Google Scholar 

  44. Trinh NH, Hoblyn J, Mohanty S, et al. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer’s disease: a meta-analysis. JAMA 2003;289:210–6.

    PubMed  CAS  Google Scholar 

  45. Morris JC. Challenging assumptions about Alzheimer’s disease; mild cognitive impairment and the cholinergic hypothesis. Ann Neurol 2002;51: 143–4.

    PubMed  Google Scholar 

  46. Davis KL, Mohs RC, Marin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer’s disease. JAMA 1999;281:1401–6.

    PubMed  CAS  Google Scholar 

  47. DeKosky ST, Ikonomovic MD, Styren SD, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002;51:145–55.

    PubMed  CAS  Google Scholar 

  48. Gilmor ML, Erickson JD, Varoqui H, et al. Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol 1999;411:693–704.

    PubMed  CAS  Google Scholar 

  49. Terry AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 2003;306:821–7.

    PubMed  CAS  Google Scholar 

  50. Mesulam M. The cholinergic lesions of Alzheimer’s disease:pivotal factor or slide show? Learn Mem 2004;11:43–9.

    PubMed  Google Scholar 

  51. Nordberg A, Alafuzoff I, Winbald B. Nicotinic and muscarinic receptor subtypes in the human brain: changes with aging and dementia. J Neurosci Res 1992;31:103–11.

    PubMed  CAS  Google Scholar 

  52. Warpman U, Alafuzoff I, Nordberg A. Coupling of muscarinic receptors to GTP proteins in postmortem human brain-alterations in Alzheimer’s disease. Neurosci Lett 1993;150:39–43.

    PubMed  CAS  Google Scholar 

  53. Rodriguez-Puertas R, Pascual J, Vilaro T, et al. Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer’s disease. Synapse 1997;26:341–50.

    PubMed  CAS  Google Scholar 

  54. Mulugeta E, Karlsson E, Islam A, et al. Loss of muscarinic M4 receptors in hippocampus of Alzheimer’s patients. Brain Res 2003;960:259–62.

    PubMed  CAS  Google Scholar 

  55. Colquhoun LM, Patrick JW. Pharmacology of neuronal nicotinic acetylcholine receptor subtypes. Adv Pharmacol 1997;39:191–20.

    Article  PubMed  CAS  Google Scholar 

  56. Drisdel RC, Green WN. Neuronal α-bungarotoxin receptors are α7 subunit homomers. J Neurosci 2000; 20:133–9.

    PubMed  CAS  Google Scholar 

  57. Nordberg A, Lundqvist H, Hartvig P, et al. Kinetic analysis of regional (S)(−)11C-nicotine binding in normal and Alzheimer’s brains—in vivo assessment using positron emission tomography. Alzheimer’s Dis Assoc Disord 1995;9:21–7.

    CAS  Google Scholar 

  58. Court J, Martin-Ruiz C, Piggott M, et al. Nicotinic receptor abnormalities in Alzheimer’s disease. Biol Psychiatry 2001;49:175–84.

    PubMed  CAS  Google Scholar 

  59. Teaktong T, Graham A, Court J, et al. Alzheimer’s disease is associated with a selective increase in γ7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia 2003;41:207–11.

    PubMed  Google Scholar 

  60. Kang J, Lemaire GH, Unterbeck A, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell surface receptor. Nature 1987;325:733–6.

    PubMed  CAS  Google Scholar 

  61. Vassar R, Bennett BD, Babu-Khan S, et al. β-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999;286:735–41.

    PubMed  CAS  Google Scholar 

  62. Kimberly WT, LaVoie MJ, Ostaszewski BL, et al. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci USA 2003;100:6382–7.

    PubMed  CAS  Google Scholar 

  63. Haass C, Steiner H. Alzheimer’s disease γ-secretase: a complex story of GxGD-type presenilin proteases. Trends Cell Biol 2002;12:556–62.

    PubMed  CAS  Google Scholar 

  64. Zhou S, Zhou H, Walian PJ, et al. CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer’s disease amyloid beta-peptide production. Proc Natl Acad Sci USA 2005;102:7499–504.

    PubMed  CAS  Google Scholar 

  65. Roberson MR, Harrell LE. Cholinergic and amyloid precursor protein metabolism. Brain Res Rev 1997;25:50–69.

    PubMed  CAS  Google Scholar 

  66. Mills J, Reiner PB. Regulation of amyloid precursor protein cleavage. J Neurochem 1999;72:443–60.

    PubMed  CAS  Google Scholar 

  67. Nitsch RM, Slack BE, Wurtman RJ, et al. Release of Alzheimer’s amyloid precursor derivatives stimulated by activation of muscarinic cholinergic receptor. Science 1992;258:304–7.

    PubMed  CAS  Google Scholar 

  68. Pittel Z, Heldman E, Barg J, et al. Muscarinic control of amyloid precursor protein secretion in rat cerebral cortex and cerebellum. Brain Res 1996;742:299–304.

    PubMed  CAS  Google Scholar 

  69. Racchi M, Mazzucchelli M, Porrello E, et al. Acetylcholinesterase inhibitors:novel activities of old molecules. Pharmacol Res 2004;50:441–51.

    PubMed  CAS  Google Scholar 

  70. Guo FF, Kumahara E, Saffen D. A CalDAGGEFI/ Rap1/B-Raf cassette couples M(1) muscarinic acetylcholine receptors to the activation of ERK1/2. J Biol Chem 2001;276:25568–81.

    PubMed  CAS  Google Scholar 

  71. Hellstrom-Lindahl E. Modulation of β-amyloid precursor protein processing and tau phosphorylation by acetylcholine receptors. Eur J Pharmacol 2000;393: 255–63.

    PubMed  CAS  Google Scholar 

  72. Manthey D, Heck S, Engert S, et al. Estrogen induces a rapid secretion of amyloid beta precursor protein via the mitogen-activated protein kinase pathway. Eur J Biochem 2001;268:4285–91.

    PubMed  CAS  Google Scholar 

  73. Kim SH, Kim YK, Jeong SJ, et al. Enhanced release of secreted form of Alzheimer’s amyloid precursor protein from PC12 cells by nicotine. Mol Pharmacol 1997;52:430–6.

    PubMed  CAS  Google Scholar 

  74. Lahiri DK, Utsuki T, Chen D, et al. Nicotine reduces the secretion of Alzheimer’s β-amyloid precursor protein containing β-amyloid peptide in the rat without altering synaptic proteins. Ann N Y Acad Sci 2002;965:364–372.

    Article  PubMed  CAS  Google Scholar 

  75. Buxbaum JD, Ruefli AA, Parker CA, et al. Calcium regulates processing of the Alzheimer’s amyloid protein precursor in a protein kinase Cindependent manner. Proc Natl Acad Sci USA 1994;91:4489–93.

    PubMed  CAS  Google Scholar 

  76. Lahiri DK, Farlow MR, Hintz N, et al. Cholinesterase inhibitors, β-amyloid precursor protein and amyloid β-peptides in Alzheimer’s disease. Acta Neurol Scand Suppl 2000;176:60–7.

    PubMed  CAS  Google Scholar 

  77. Racchi M, Govoni S. The pharmacology of amyloid precursor protein processing. Exp Gerontology 2003;38:145–57.

    CAS  Google Scholar 

  78. Zimmermann M, Gardoni F, Marcello E, et al., Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines. J Neurochem 2004;90:1489–99.

    PubMed  CAS  Google Scholar 

  79. Zimmermann M, Borroni B, Cattabeni F, et al. Cholinesterase inhibitors influence APP metabolism in Alzheimer’s disease patients. Neurobiol Dis 2005;19:237–42.

    PubMed  CAS  Google Scholar 

  80. Mori F, Lai CC, Fusi F, et al. Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. NeuroReport 1995;6:633–6.

    Article  PubMed  CAS  Google Scholar 

  81. Lahiri DK, Farlow MR, Sambamurti K. The secretion of amyloid beta-peptides is inhibited in the tacrine-treated human neuroblastoma cells. Mol Brain Res 1998;62:131–40.

    PubMed  CAS  Google Scholar 

  82. Shaw KT, Utsuki T, Rogers J, et al. Phenserine regulates translation of beta-amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development. Proc Natl Acad Sci USA 2001;98:7605–10.

    PubMed  CAS  Google Scholar 

  83. Auld DS, Kornecook TJ, Bastianetto S, et al. Alzheimer’s disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002;68:209–45

    PubMed  CAS  Google Scholar 

  84. Jhamandas JH, Cho C, Jassar B, et al. Cellular mechanisms for amyloid β-protein activation of rat basal forebrain neurons. J Neurophysiol 2001;86: 1312–20.

    PubMed  CAS  Google Scholar 

  85. Dolezal V, Kasparova J. β-amyloid and cholinergic neurons. Neurochem Res 2003;28:499–506.

    PubMed  CAS  Google Scholar 

  86. Kar S, Slowikowski SP, Westaway, Mount HT. Interactions between b-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. J Psychiatry Neurosci 2004;29:427–41.

    PubMed  Google Scholar 

  87. Kar S, Seto D, Gaudreau P, et al. β-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal formation. J Neurosci 1996;16:1034–40.

    PubMed  CAS  Google Scholar 

  88. Kar S, Issa AM, Seto D, et al. Amyloid β-peptide inhibits high-affinity choline uptake and acetylcholine release in rat hippocampal slices. J Neurochem 1998;70:2179–87.

    Article  PubMed  CAS  Google Scholar 

  89. Wang HY, Wild KD, Shank RP, et al. Galanin inhibits acetylcholine release from rat cerebral cortex via a pertussis toxin-sensitive Gi protein. Neuropeptides 1999;33:197–205.

    PubMed  CAS  Google Scholar 

  90. Melo JB, Agostinho P, Oliveira CR. Amyloid betapeptide 25–35 reduces [3H]acetylcholine release in retinal neurons. Involvement of metabolic dysfunction. Amyloid 2002;9:221–8.

    PubMed  CAS  Google Scholar 

  91. Satoh Y, Hirakura Y, Shibayama S, et al. Betaamyloid peptides inhibit acetylcholine release from cholinergic nerve endings isolated from an electric ray. Neurosci Lett 2001;302:97–100.

    PubMed  CAS  Google Scholar 

  92. Vaucher E, Amount N, Rowe W, et al. Amyloid β peptide levels and its effects on hippocampal acetylcholine release in aged, cognitively-impaired and-unimpaired rats. J Chem Neuroanat 2001;21:323–9.

    PubMed  CAS  Google Scholar 

  93. Farr SA, Banks WA, Uezy K, et al. Antibody to β-amyloid protein increases acetylcholine in the hippocampus of 12 month SAMP8 male mice. Life Sci 2003;73:555–62.

    PubMed  CAS  Google Scholar 

  94. Lee TF, Shiao YJ, Chen CF, et al. Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices. Planta Med 2001;67:634–7.

    PubMed  CAS  Google Scholar 

  95. Lee T, Chen C, Wang AC. Effect of Ginkolides on β-amyloid-suppressed acetylcholine release from rat hippocampal slices. Phytother Res 2004;18: 556–60.

    PubMed  CAS  Google Scholar 

  96. Wecker L. The synthesis and release of acetylcholine by depolarized hippocampal slices is increased by increased choline available in vitro prior to stimulation. J Neurochem 1991;57:1119–27.

    PubMed  CAS  Google Scholar 

  97. Zambrzycka A, Alberghina M, Strosznajder JB. Effects of aging and amyloid-beta peptides on choline acetyltransferase activity in rat brain. Neurochem Res 2002;27:277–81.

    PubMed  CAS  Google Scholar 

  98. Dobransky T, Brewer D, Lajoie G, et al. Phosphorylation of 69-kDa choline acetyltransferase at threonine 456 in response to amyloid-beta peptide 1–42. J Biol Chem 2003;278:5883–93.

    PubMed  CAS  Google Scholar 

  99. Kristofikova Z, Tekalova H, Klaschka J. Amyloid beta peptide1–40 and the function of rat hippocampal hemicholinium-3 sensitive choline carriers: effects of a proteolytic degradation in vitro. Neurochem Res 2001;26:203–12.

    PubMed  CAS  Google Scholar 

  100. Pedersen WA, Kloczewiak MA, Blusztajn JK. Amyloid β-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurones of the basal forebrain. Proc Natl Acad Sci USA 1996;93:8068–71.

    PubMed  CAS  Google Scholar 

  101. Pedersen WA, Blusztajn JK. Characterization of the acetylcholine reducing effect of the amyloid-beta peptide in mouse SN56 cells. Neurosci Lett 1997;239:77–80.

    PubMed  CAS  Google Scholar 

  102. Hoshi M, Takashima A, Murayama M, et al. Nontoxic amyloid β peptide1–42 supresses acetylcholine synthesis. J Biol Chem 1997;272:2038–41.

    PubMed  CAS  Google Scholar 

  103. Jhamandas JH, Harris KH, Cho C, et al. Human amylin actions on rat cholinergic basal forebrain neurons: antagonism of beta-amyloid effects. J Neurophysiol 2003;89:2923–30.

    PubMed  CAS  Google Scholar 

  104. Joslin G, Krause JE, Hershey AD, et al. Amyloid-β peptide, substance, and bombesin bind to the serpin-enzyme complex receptor. J Biol Chem 1991; 266:21897–902.

    PubMed  CAS  Google Scholar 

  105. El Khoury J, Hickman SE, Thomas CA, et al. Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils. Nature 1996;382:716–9.

    PubMed  Google Scholar 

  106. Yan SD, Chen X, Fu J, et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer’s disease. Nature 1996;382:685–91.

    PubMed  CAS  Google Scholar 

  107. Kuner P, Schubenel R, Hertel C. β-amyloid binds to p75NTR and activates NF B in human neuroblastoma cells. J Neurosci Res 1998;54:798–804.

    PubMed  CAS  Google Scholar 

  108. Wang HY, Lee DHS, D’Andrea MR, et al. β-amyloid1–42 binds γ7 nicotinic acetylcholine receptor with high affinity: implications for Alzheimer’s disease pathology. J Biol Chem 2000; 275: 5626–32.

    PubMed  CAS  Google Scholar 

  109. Wang HY, Lee DHS, Davis CB, et al. Amyloid peptide Aβ1–42 binds selectively and with picomolar affinity to γ7 nicotinic acetylcholine receptors. J Neurochem 2000;75:1155–61.

    PubMed  CAS  Google Scholar 

  110. Liu Q, Kawai H, Berg DK. β-amyloid peptide blocks the response of γ7-containing nicotinic receptors on hippocampal neurons. Proc Natl Acad Sci USA 2001;98:4734–9.

    PubMed  CAS  Google Scholar 

  111. Pettit DL, Shao Z, Yakel JL. β-amyloid1–42 peptide directly modulates nicotinic receptors in the rat hippocampal slice. J Neurosci 2001;21:RC120–24.

    Google Scholar 

  112. Tozaki H, Matsumoto A, Kanno T, et al. The inhibitory and facilitatory actions of amyloid-beta peptides on nicotinic ACh receptors and AMPA receptors. Biochem Biophys Res Commun 2002; 294:42–5.

    PubMed  CAS  Google Scholar 

  113. Grassi F, Palma E, Tonini R, et al. Amyloid beta(1–42) peptide alters the gating of human and mouse alpha-bungarotoxin-sensitive nicotinic receptors. J Physiol 2003;547:147–57.

    PubMed  CAS  Google Scholar 

  114. Wu J, Kuo YP, George AA, et al. β-amyloid directly inhibits α4β2-nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells. J Biol Chem 2004;279:37842–51.

    PubMed  CAS  Google Scholar 

  115. Dineley KT, Bell K, Bui D, et al. beta-Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Biol Chem 2002;277:25056–61.

    PubMed  CAS  Google Scholar 

  116. Fu W, Jhamandas JH. Beta-amyloid peptide activates non-alpha7 nicotinic acetylcholine receptors in rat basal forebrain neurons. J Neurophysiol 2003;90:3130–6.

    PubMed  CAS  Google Scholar 

  117. Nagele RG, D’Andrea MR, Anderson WJ, et al. Intracellular accumulation of beta-amyloid(1–42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience 2002;110:199–211

    PubMed  CAS  Google Scholar 

  118. Wang HY, Li W, Benedetti NJ, et al. α7 nicotinic acetylcholine receptors mediate β-amyloid peptideinduced tau protein phosphorylation. J Biol Chem 2003;278:31547–53.

    PubMed  CAS  Google Scholar 

  119. Lee DHS, Wang HY. Differential physiologic responses of α7 nicotinic acetylcholine receptors to β-amyloid1–40 and β-amyloid1–42. J Neurobiol 2003;55:25–30.

    PubMed  CAS  Google Scholar 

  120. Kelly JF, Furukawa K, Barger SW, et al. Amyloid β-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons. Proc Natl Acad Sci USA 1996;93:6753–8.

    PubMed  CAS  Google Scholar 

  121. Huang HM, Ou HC, Hsieh SJ. Amyloid beta peptide impaired carbachol but not glutamate-mediated phosphoinositide pathways in cultured rat cortical neurons. Neurochem Res 2000;25:303–12.

    PubMed  CAS  Google Scholar 

  122. Selkoe DJ, Schenk D. Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 2003;43: 545–84.

    PubMed  CAS  Google Scholar 

  123. Pike CJ, Cotman CW. Cultured GABA-immunoreactive neurons are resistant to toxicity induced by β-amyloid. Neuroscience 1993;56:269–74.

    PubMed  CAS  Google Scholar 

  124. Olesen OF, Dago L, Mikkelsen JD. Amyloid β neurotoxicity in the cholinergic but not in the serotonergic phenotype of RN46A cells. Mol Brain Res 1998;57:266–74.

    PubMed  CAS  Google Scholar 

  125. Le W, Xie WJ, Kong R, et al. β-amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression β-amyloid precursor protein. J Neurochem 1997; 69:978–85.

    Article  PubMed  CAS  Google Scholar 

  126. Zheng WH, Bastianetto S, Mennicken F, et al. Amyloid β peptide induces tau phosphorylation and neuronal degeneration in rat primary septal cultured neurons. Neuroscience 2002;115:201–11.

    PubMed  CAS  Google Scholar 

  127. Jhamandas JH, MacTavish D. Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons. J Neurosci 2004;24:5579–84.

    PubMed  CAS  Google Scholar 

  128. Jhamandas JH, Wie MB, Harris K, et al. Fucoidan inhibits cellular and neurotoxic effects of beta-amyloid (A beta) in rat cholinergic basal forebrain neurons. Eur J Neurosci 2005;21:2649–59.

    PubMed  Google Scholar 

  129. Behl C, Cole GM, Schubert D. Vitamin E protects nerve cells from amyloid β protein toxicity. Biochem Biophys Res Commun 1992;186:944–50.

    PubMed  CAS  Google Scholar 

  130. Mattson MP, Cheng B, Davis D, et al. β-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 1992;12:376–89.

    PubMed  CAS  Google Scholar 

  131. Hensley K, Carney JM, Mattson MP, et al. A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer’s disease. Proc Natl Acad Sci USA 1994;91:3270–74.

    PubMed  CAS  Google Scholar 

  132. Perini G, Della-Bianca V, Politi V, et al. Role of p75 neurotrophin receptor in the neurotoxicity by betaamyloid peptides and synergistic effect of inflammatory cytokines. J Exp Med 2002;195:907–18

    PubMed  CAS  Google Scholar 

  133. Zhang Y, Hong Y, Bounhar Y, et al., p75 neurotrophin receptor protects primary cultures of human neurons against extracellular amyloid beta peptide cytotoxicity. J Neurosci 2003;23:7385–94.

    PubMed  CAS  Google Scholar 

  134. Busciglio J, Lorenzo A, Yeh J, et al. β-amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 1995;14:879–88.

    PubMed  CAS  Google Scholar 

  135. Shea TB, Prabhakar S, Ekinci FJ. β-amyloid and ionophore A23187 evoke tau hyper-phosphorylation by distinct intracellular pathways: differential involvement of the calpain/protein kinase C system. J Neurosci Res 1997;49:759–68.

    PubMed  CAS  Google Scholar 

  136. Alvarez G, Munoz-Montano JR, et al. Lithium protects cultured neurons against β-amyloid-induced neurodegeneration. FEBS Lett 1999;453:260–64.

    PubMed  CAS  Google Scholar 

  137. Mark RJ, Lovell MA, Markesbery WR, et al. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid β-peptide. J Neurochem 1997;68:255–64.

    Article  PubMed  CAS  Google Scholar 

  138. Greenberg SM, Kosik KS. Secreted β-APP stimulates MAP kinase and phosphorylation of tau in neurons. Neurobiol Aging 1995;16:403–8.

    PubMed  CAS  Google Scholar 

  139. Takashima A, Honda T, Yasutake K, et al. Activation of tau protein kinase I/glycogen synthase kinase-3 beta by amyloid beta peptide (25–35) enhances phosphorylation of tau in hippocampal neurons. Neurosci Res 1998;4:317–23.

    Google Scholar 

  140. Alvarez A, Toro R, Caceres A, et al. Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death. FEBS Lett 2001;459:421–6.

    Google Scholar 

  141. Hong M, Chen DCR, Klein PS, et al. Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3.J Biol Chem 1997;40:25326–32.

    Google Scholar 

  142. Sadot E, Gurwitz D, Barg J, et al. Activation of m1 muscarinic acetylcholine receptor regulates τ phosphorylation in transfected PC12 cells. J Neurochem 1996;66:877–80.

    Article  PubMed  CAS  Google Scholar 

  143. Hellstrom-Lindahl E, Moore H, Nordberg A. Increased levels of tau protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists. J Neurochem 2000;74:777–84.

    PubMed  CAS  Google Scholar 

  144. Yamaguchi Y, Kawashima S, Effects of amyloidbeta-( 25–35) on passive avoidance, radial-arm maze learning and choline acetyltransferase activity in the rat. Eur J Pharmacol 2001;412:265–72.

    PubMed  CAS  Google Scholar 

  145. Gonzalo-Ruiz A, Sang JM, Arevalo J, Amyloid beta peptide-induced cholinergic fibres loss in the cerebral cortex of the rat is modified by diet high in lipids and by age. J Chem Neuroanat 2005;29:31–48.

    PubMed  CAS  Google Scholar 

  146. Abe E, Casamenti F, Giovannelli L, et al. Administration of amyloid β-peptides into the medial septum of rats decreases acetylcholine release from hippocampus in vivo. Brain Res 1994; 636:162–4.

    PubMed  CAS  Google Scholar 

  147. Giovannini MG, Scali C, Prosperi C, et al. Betaamyloid-induced inflammation and cholinergic hypofunction in the rat brain in vivo: involvement of the p38MAPK pathway. Neurobiol Dis 2002;11:257–74.

    PubMed  CAS  Google Scholar 

  148. Boncristiano S, Calhoun ME, Kelly PH, et al. Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. J Neurosci 2002;22:3234–43.

    PubMed  CAS  Google Scholar 

  149. Bronfman FC, Moechars D, Van Leuven F. Acetylcholinesterase-positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein london mutant transgenic mice. Neurobiol Dis 2000;7:152–68.

    PubMed  CAS  Google Scholar 

  150. Wong TP, Debeir T, Duff K, et al. Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J Neurosci 1999;19:2706–16.

    PubMed  CAS  Google Scholar 

  151. Jaffar S, Counts SE, Ma SY, et al. Neuropathology of mice carrying mutant APPswe and/or PS1M146L transgenes: alterations in the p75NTR cholinergic basal forebrain septohippocampal pathway. Exp Neurol 2001;170:227–43.

    PubMed  CAS  Google Scholar 

  152. Gau JT, Steinhilb ML, Kao TC, et al. Stable β-secretase activity and presynaptic cholinergic markers during progressive central nervous system amyloidogenesis in Tg2576 mice. Am J Pathol 2002;160:731–8.

    PubMed  CAS  Google Scholar 

  153. Vaucher E, Fluit P, Chishti MA, et al. Alteration in working memory but not cholinergic receptor binding sites in transgenic mice expressing human presenilin 1 transgenes. Exp Neurol 2002;21:323–9.

    Google Scholar 

  154. Dineley KT, Xia X, Bui D, et al. Accelerated plaque accumulation, associative learning deficits and upregulation of α7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J Biol Chem 2002;227:22768–80.

    Google Scholar 

  155. Chishti MA, Yang DS, Janus C, et al. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 2001;276:21562–70.

    PubMed  CAS  Google Scholar 

  156. Slowikowski SPM, Chishti MA, Zheng WH, et al. Alterations in cholinergic parameters in the hippocampus of transgenic mice expressing mutated amyloid precursor protein and/or presenilin-1 transgenes. Soc Neurosci Abs 2002;295.18.

    Google Scholar 

  157. Apelt J, Kumar A, Schliebs R. Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish mutation of human beta-amyloid precursor protein. Brain Res 2002;953:17–30.

    PubMed  CAS  Google Scholar 

  158. Hernandez D, Sugaya K, Qu T, et al. Survival and plasticity of basal forebrain cholinergic system in mice transgenic for presenilin-1 and amyloid precursor protein mutant genes. NeuroReport 2001; 12:1377–84.

    PubMed  CAS  Google Scholar 

  159. German DC, Yazdani U, Speciale SG, et al. Cholinergic neuropathology in a mouse model of Alzheimer’s disease. J Comp Neurol 2003;462:371–81.

    PubMed  Google Scholar 

  160. Hu L, Wong TP, Cote SL, et al. The impact of A-plaques on cortical cholinergic and non-cholinergic presynaptic boutons in Alzheimer’s disease-like transgenic mice. Neuroscience 2003;121:421–32.

    PubMed  CAS  Google Scholar 

  161. Feng Z, Chang Y, Cheng Y, et al. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer’s disease. J Pineal Res 2004;37:129–36.

    PubMed  CAS  Google Scholar 

  162. Klingner M, Apelt J, Kumar A, Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology. Int J Dev Neurosci 2003;21:357–69.

    PubMed  CAS  Google Scholar 

  163. Oddo S, Caccamo A, Green KN, et al. Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer’s disease. Proc Natl Acad Sci USA 2005;102:3046–3051.

    PubMed  CAS  Google Scholar 

  164. Hartmann J, Erb C, Ebert U, et al., Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice. Neuroscience 2004;125:1009–17.

    PubMed  CAS  Google Scholar 

  165. Haass C, Schlossmacher MG, Hung AY, et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 1992;359:322–5.

    PubMed  CAS  Google Scholar 

  166. Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 1992;359:325–7.

    PubMed  CAS  Google Scholar 

  167. Shoji M, Golde TE, Ghiso J, et al. Production of Alzheimer’s β protein by normal proteolytic processing. Science 1992;258:126–9.

    PubMed  CAS  Google Scholar 

  168. Iverfeldt K, Walaas SI, Greengard P. Altered processing of Alzheimer’s amyloid precursor protein in response to neuronal degeneration. Proc Natl Acad Sci USA 1993;90:4146–50.

    PubMed  CAS  Google Scholar 

  169. Wallace W, Ahlers ST, Gotlib J, et al. Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA 1993;90:8712–6.

    PubMed  CAS  Google Scholar 

  170. Lin L, Georgievska B, Mattsson A, et al. Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation. Proc Natl Acad. Sci USA 1999;96:12108–13.

    PubMed  CAS  Google Scholar 

  171. Buxbaum JD, Oishi M, Chen HI, et al. Cholinergic agonists and interleukin 1 regulate processing and secretion of the β/A4 amyloid precursor protein. Proc Natl Acad Sci USA 1992;89:10075–8.

    PubMed  CAS  Google Scholar 

  172. Allen DD, Galdzicki Z, Brining SK, et al. Beta-amyloid induced increase in choline flux across PC12 cell membranes. Neurosci Lett 1997;234:71–3.

    PubMed  CAS  Google Scholar 

  173. Wurtman R. Choline metabolism as a basis for the selective vulnerability of cholinergic neurones. Trends Neurosci 1992;15:117–22.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine (Neurology) and Psychiatry, University of Alberta, Edmonton, AB, Canada

    Satyabrata Karn PhD

  2. Department of Psychiatry, University of Alberta, Edmonton, AB, Canada

    Z. Wei PhD, Doreen Kabogo BSc & Mee-Sook Song PhD

  3. Department of Neurology, University of Alberta, Edmonton, AB, Canada

    David MacTavish Dls & Jack H. Jhamandas MD, PhD

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  1. Satyabrata Karn PhD
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  1. Research and Development, Ocean Nutrition Canada, Dartmouth, Nova Scotia, Canada

    Colin J. Barrow BSc (Hons),PhD, MBA (Vice President) (Vice President)

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    David H. Small BSc, PhD (Associate Professorial Fellow) (Associate Professorial Fellow)

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Karn, S., Wei, Z., MacTavish, D., Kabogo, D., Song, MS., Jhamandas, J.H. (2007). Amyloid β-Peptide and Central Cholinergic Neurons: Involvement in Normal Brain Function and Alzheimer’s Disease Pathology. In: Barrow, C.J., Small, D.H. (eds) Abeta Peptide and Alzheimer’s Disease. Springer, London. https://doi.org/10.1007/978-1-84628-440-3_10

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