β-Amyloid: A disease target or a synaptic regulator affecting age-related neurotransmitter changes?

Current Pharmaceutical Design

Volumn 16, Issue 6, 2010, Pages 672-683

  Mura, E ^a   Lanni, C ^a   Preda, S ^a   Pistoia, F ^b,c   Sara M ^b   Racchi, M ^a   Schettini, G ^d   Marchi, M ^d   Govoni, S ^a  

^a UNIVERSITY OF PAVIA   (Italy)

^b Istituto San Raffaele   (Italy)

^c UNIVERSITY OF L'AQUILA   (Italy)

^d UNIVERSITY OF GENOA   (Italy)

Author keywords

amyloid; Aging; Alzheimer's disease; Neurogenesis; Neurotransmitters; Physiological role; Retrogenesis; Synaptic activity

Indexed keywords

3,4 DIAMINOPYRIDINE; AMBENONIUM; AMYLOID BETA PROTEIN; DONEPEZIL; GALANTAMINE; GANSTIGMINE; HEPTYLPHYSOSTIGMINE; METRIFONATE; NEUROTRANSMITTER; PHENSERINE; PHYSOSTIGMINE; RIVASTIGMINE; TACRINE; TARENFLURBIL; UNCLASSIFIED DRUG; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; DRUG;

AGING; ALZHEIMER DISEASE; BEHAVIOR DISORDER; BRAIN DEVELOPMENT; BRAIN REGION; CLINICAL TRIAL; COGNITION; DEGENERATIVE DISEASE; GLAUCOMA; HUMAN; LIVER DISEASE; LONG TERM DEPRESSION; LONG TERM POTENTIATION; MULTIPLE SCLEROSIS; MYASTHENIA GRAVIS; NERVOUS SYSTEM DEVELOPMENT; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN METABOLISM; REVIEW; SYNAPTIC MEMBRANE; SYNAPTIC TRANSMISSION; ANIMAL; COMPARATIVE STUDY; DRUG DELIVERY SYSTEM; DRUG EFFECTS; METABOLISM; PHYSIOLOGY; SYNAPSE; TRENDS;

AGING; AMYLOID BETA-PROTEIN; ANIMALS; DRUG DELIVERY SYSTEMS; HUMANS; NEUROTRANSMITTER AGENTS; PHARMACEUTICAL PREPARATIONS; SYNAPSES; SYNAPTIC TRANSMISSION; AMYLOID BETA-PEPTIDES;

EID: 77950226048     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210790883723     Document Type: Review

References (130)

1. Wang XP, Ding HL. Alzheimer's disease: epidemiology, genetics, and beyond. Neurosci Bull 2008; 24: 105-109
2. Gasparini L, Racchi M, Binetti G, Trabucchi M, Solerte SB, Alkon D, et al. Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease. FASEB J 1998; 12: 17-34.
3. Racchi M, Govoni S. Rationalizing a pharmacological intervention on the amyloid precursor protein metabolism. TIPS 1999; 20: 418-423
4. Racchi M, Mazzucchelli M, Porrello E, Lanni C, Govoni S. Acetylcholinesterase inhibitors: novel activities of old molecules. Pharmacol Res 2004; 4: 441-451
5. Yamin G, Ono K, Inayathullah M, Teplow DB. Amyloid β-protein assembly as a therapeutic target of Alzheimer's disease. Curr Pharm Des 2008; 14: 3231-3246
6. Schmechel DE, Goldgaber D, Burkhart DS, Gilbert JR, Gajdusek DC, Roses AD. Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer disease. Alzheimer Dis Assoc Disord 1998; 2: 96-111.
7. Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, et al. β-amyloid precursor protein of Alzheimer disease occurs as 110-135-kilodalton membrane-associated proteins in neural and non-neural tissues. Proc Natl Acad Sci USA 1988; 85: 7341-7345
8. Tanaka S, Shiojiri S, Takahashi Y, Kitaguchi N, Ito H, Kameyama M, et al. Tissue-specific expression of three types of β-protein precursor mRNA: enhancement of protease inhibitor-harboring types in Alzheimer's disease brain. Biochem Biophys Res Commun 1989; 165: 1406-1414
9. Nunan J, Small DH. Regulation of APP cleavage by α-, β-and γ-secretases. FEBS Lett 2000; 483: 6-10.
10. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001; 81: 741-766
11. Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ. β-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 1993; 268: 3021-3024
12. Fischer A. Cholinergic treatments with emphasis on M1 muscarinic agonists as potential disease-modifying agents for Alzheimer's disease. Neurotherapeutics 2008; 5: 433-442
13. Thinakaran G, Koo EH. Amyloid precursor protein trafficking, processing, and function. J Biol Chem 2008; 283: 29615-29619
14. Passer B, Pellegrini L, Russo C, Siegel RM, Lenardo MJ, Schettini G, et al. Generation of an apoptotic intracellular peptide by γ-secretase cleavage of Alzheimer's amyloid β protein precursor. J Alzheimer's Dis 2000; 2: 289-301.
15. Turner PR, O'Connor K, Tate WP, Abrahamb WC. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 2003; 70: 1-32.
16. Trapp BD, Hauer PE. Amyloid precursor protein is enriched in radial glia-implications for neuronal development. J Neurosci Res 1994; 37: 538-550
17. Gralle M, Ferreira S. Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Prog Neurobiol 2007; 82: 11-32.
18. Galvan V, Gorostiza OF, Banwait S, Ataie M, Logvinova AV, Sitaraman S, et al. Reversal of Alzheimer's-like pathology and behaviour in human APP transgenic mice by mutation of Asp664. Proc Natl Acad Sci USA 2006; 103: 7130-7135
19. Chen CW, Boiteau RM, Lai WF, Barger SW, Cataldo AM. sAPPα enhances the transdifferentiation of adult bone marrow progenitor cells to neuronal phenotypes. Curr Alzheimer Res 2006; 3: 63-70.
20. Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Nakamura Y, Kohsaka S. Novel domain-specific actions of amyloid precursor protein on developing synapses. J Neurosci 1998; 18: 9386-9393
21. Szczepanik AM, Rampe D, Ringheim GE. Amyloid-β peptide fragments p3 and p4 induce pro-inflammatory cytokine and chemokine production in vitro and in vivo. J Neurochem 2001; 77: 304-317
22. Russo C, Venezia V, Repetto E, Nizzari M, Violani E, Carlo P, et al. The amyloid precursor protein and its network of interacting proteins: physiological and pathological implications. Brain Res Brain Res Rev 2005; 48: 257-264
23. Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885-890
24. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256: 184-185
25. Kirkitadze MD, Kowalska A. Molecular mechanisms initiating amyloid β-fibril formation in Alzheimer's disease. Acta Biochim Polym 2005; 52: 417-423
26. Sabella S, Quaglia M, Lanni C, Racchi M, Govoni S, Caccialanza G, et al. Capillary electrophoresis studies on the aggregation process of β-amyloid 1-42 and 1-40 peptides. Electrophoresis 2004; 25: 3186-3194
27. Watson D, Castaño E, Kokjohn TA, Kuo YM, Lyubchenko Y, Pinsky D, et al. Physicochemical characteristics of soluble oligomeric Aβ and their pathologic role in Alzheimer's disease. Neurol Res 2005; 27: 869-881
28. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 2008; 14: 837-842
29. Dimakopoulos AC. Protein aggregation in Alzheimer's disease and other neoropathological disorders. Curr Alzheimer Res 2005; 2: 19-28.
30. Verdile G, Fuller S, Atwood CS, Laws SM, Gandy SE, Martins RN. The role of β amyloid in Alzheimer's disease: still a cause of everything or the only one who got caught? Pharmacol Res 2004; 50: 397-409.
31. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, et al. APP processing and synaptic function. Neuron 2003; 37: 925-937
32. Terai K, Iwai A, Kawabata S, Tasaki Y, Watanabe T, Miyata K, et al. Amyloid-deposits in transgenic mice expressing human βamyloid precursor protein have the same characteristics as those in Alzheimer's disease. Neuroscience 2001; 104: 299-310.
33. Walsh DM, Selkoe DJ. Aβ Oligomers-a decade of discovery. J Neurochem 2007; 101: 1172-1184
34. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB. Amyloid β -protein (Aβ) assembly: abeta 40 and Aβ 42 oligomerize through distinct pathways. Proc Natl Acad Sci USA 2003; 100: 330-335
35. Zou K, Kim D, Kakio A, Byun K, Gong JS, Kim J, et al. Amyloid β-protein (Aβ)1-40 protects neurons from damage induced by Aβ1-42 in culture and in rat brain. J Neurochem 2003; 87: 609-619
36. Mayeux R, Tang MX, Jacobs DM, Manly J, Bell K, Merchant C, et al. Plasma amyloid β-peptide 1-42 and incipient Alzheimer's disease. Ann Neurol 1999; 46: 412-416
37. Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid based therapeutics. Annu Rev Pharmacol Toxicol 2003; 43: 545-584
38. Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 1992; 359: 322-325
39. Tamaoka A, Sawamura N, Fukushima T, Shoji S, Matsubara E, Shoji M, et al. Amyloid β protein 42 (43) in cerebrospinal fluid of patients with Alzheimer's disease. J Neurol Sci 1997; 148: 41-45
40. Kontush A, Berndt C, Weber W, Akopyan V, Arlt S, Schippling S, et al. Amyloid-β is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Rad Biol Medic 2001; 30: 119-128
41. Grimm MO, Grimm HS, Hartmann T. Amyloid β as a regulator of lipid homeostasis. Trends Mol Med 2007; 13: 337-344
42. Ida N, Hartmann T, Pantel J, Schröder J, Zerfass R, Förstl H, et al. Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. J Biol Chem 1996; 271: 22908-22914
43. Shoji M, Kanai M, Matsubara E, Tomidokoro Y, Shizuka M, Ikeda Y, et al. The levels of cerebrospinal fluid Aβ40 and Aβ42(43) are regulated age-dependently. Neurobiol Aging 2001; 22: 209-215
44. Cirrito JR, May PC, O'Dell MA, Taylor JW, Parsadanian M, Cramer JW, et al. In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-β metabolism and half-life. J Neurosci 2003; 23: 8844-8853
45. Brody DL, Magnoni S, Schwetye KE, Spinner ML, Esparza TJ, Stocchetti N, et al. Amyloid-β dynamics correlate with neurological status in the injured human brain. Science 2008; 321: 1221-1224
46. Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996; 16: 2027-2033
47. Sharp FR, Liu J, Bernabeu R. Neurogenesis following brain ischemia. Brain Res Dev Brain Res 2002; 134: 23-30.
48. Ribak CE, Dashtipour K. Neuroplasticity in the damaged dentate gyrus of the epileptic brain. Prog Brain Res 2002; 136: 319-328
49. Henn FA, Vollmayr B. Neurogenesis and depression: etiology or epiphenomenon? Biol Psychiatry 2004; 56: 146-150
50. Bacon Moore AS, Paulsen JS, Murphy C. A test of odor fluency in patients with Alzheimer's and Huntington's disease. J Clin Exp Neuropsychol 1999; 21: 341-351
51. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, et al. Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci USA 2004; 101: 343-347
52. Lopez-Toledano MA, Shelanski ML. Neurogenic effect of β amyloid peptide in the development of neural stem cells. J Neurosci 2004; 24: 5439-5444
53. Heo C, Chang KA, Soon Choi H, Kim HS, Kim S, Liew H, et al. Effects of the monomeric, oligomeric, and fibrillar Aβ42 peptides on the proliferation and differentiation of adult neural stem cells from subventricular zone. J Neurochem 2007; 102: 493-500.
54. Chen Y, Dong C. Aβ40 promotes neuronal cell fate in neural progenitor cells. Cell Death Differ 2009; 16: 386-394
55. Mazur-Kolecka B, Golabek A, Nowicki K, Flory M, Frackowiak J. Amyloid-β impairs development of neuronal progenitor cells by oxidative mechanisms. Neurobiol Aging 2006; 27: 1181-1192
56. Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA. The production of amyloid β peptide is a critical requirement for the viability of central neurons. J Neurosci 2003; 23: 5531-5535
57. Mehta PD, Pirttila T, Patrick BA, Barshatzky M, Mehta SP. Amyloid β protein 1-40 and 1-42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease. Neurosci Lett 2001; 304: 102-106
58. Katz LC, Shatz CJ. Synaptic activity and the construction of cortical circuits. Science 1996; 274; 1133-1138
59. Verhage M, Maia AS, Plomp JJ, Brussaard AB, Heeroma JH, Vermeer H, et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 2000; 287; 864-869
60. Reisberg B, Franssen EH, Souren LE, Auer SR, Akram I, Kenowsky S. Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: management and treatment import. Am J Alzheimers Dis Other Demen 2002; 17: 202-212
61. Megias M, Emri Z, Freund TF, Gulyas AI. Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience 2001; 102: 527-540
62. Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 2000; 23: 649-711.
63. Gustafsson B, Wigstrom H. Physiological mechanisms underlying long-term potentiation. Trends Neurosci 1988; 11: 156-162
64. Malinow R, Malenka RC. AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 2002; 25: 103-126
65. Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, et al. AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice. Proc Natl Acad Sci USA 2006; 103: 3410-3415
66. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, et al. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 1999; 2: 271-276
67. Knobloch M, Farinelli M, Konietzko U, Nitsch RM, Mansuy IM. Aβ oligomer-mediated long-term potentiation impairment involves protein phosphatase 1-dependent mechanisms. J Neurosci 2007; 27: 7648-7653
68. Ting JT, Kelley BG, Lambert TJ, Cook DG, Sullivan JM. Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc Natl Acad Sci USA 2007; 104: 353-358
69. Wasling P, Daborg J, Riebe I, Andersson M, Portelius E, Blennow K, et al. Synaptic retrogenesis and amyloid-β in Alzheimer's Disease. J Alzheimer Dis 2009; 16: 1-14.
70. Ribaut-Barassin C, Dupont JL, Haeberle AM, Bombarde G, Huber G, Moussaoui S, et al. Alzheimer's disease proteins in cerebellar and hippocampal synapses during postnatal development and aging of the rat. Neuroscience 2003; 120: 405-423
71. Chiocco MJ, Lamb BT. Spatial and temporal control of age-related APP processing in genomic-based beta-secretase transgenic mice. Neurobiol Aging 2007; 28: 75-84.
72. Yan XX, Li T, Rominger CM, Prakash SR, Wong PC, Olson RE, et al. Binding sites of gammasecretase inhibitors in rodent brain: distribution, postnatal development, and effect of deafferentation. J Neurosci 2004; 24: 2942-2952
73. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptordependent signaling pathway. J Neurosci 2007; 27: 2866-2875
74. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci 2006; 26: 7212-7221
75. Lazarov O, Lee M, Peterson DA, Sisodia SS. Evidence that synaptically released β-amyloid accumulates as extracellular deposits in the hippocampus of transgenic mice. J Neurosci 2002; 22: 9785-9793
76. Zhong P, Gu Z, Wang X, Jiang H, Feng J, Yan Z. Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. J Biol Chem 2003; 278: 26888-26896
77. Preda S, Govoni S, Lanni C, Racchi M, Mura E, Grilli M, et al. Acute β-amyloid administration disrupts the cholinergic control of dopamine release in the nucleus accumbens. Neuropsychopharmacology 2008; 33: 1062-1070
78. Weiss JH, Pike CJ, Cotman CW. Ca2+ channel blockers attenuate β-amyloid peptide toxicity to cortical neurons in culture. J Neurochem 1994; 62: 372-375
79. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K. Amyloid β protein potentiates Ca2+ influx through L-type voltage-sensitive Ca channels: a possible involvement of free radicals. J Neurochem 1997; 68: 265-271
80. Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW. Neurodegeneration induced by β-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci 1993; 13: 1676-1687
81. Ramsden M, Henderson Z, Pearson HA. Modulation of Ca++ channel currents in primary cultures of rat cortical neurones by amyloid β protein (1-40) is dependent on solubility status. Brain Res 2002; 956: 254-261
82. Ramsden M, Plant LD, Webster NJ, Vaughan PF, Henderson Z, Pearson HA. Differential effects of unaggregated and aggregated amyloid β protein (1-40) on K(+) channel currents in primary cultures of rat cerebellar granule and cortical neurones. J Neurochem 2001; 79: 699-712.
83. Plant LD, Webster NJ, Boyle JP, Ramsden M, Freir DB, Peers C, et al. Amyloid β peptide as a physiological modulator of neuronal 'A'-type K+ current. Neurobiol Aging 2006; 27: 1673-1683
84. Kerrigan TL, Atkinson L, Peers C, Pearson HA. Modulation of 'A'-type K+ current by rodent and human forms of amyloid β protein. Neuroreport 2008; 19: 839-843
85. Peña F, Gutiérrez-Lerma A, Quiroz-Baez R, Arias C. The role of β-amyloid protein in synaptic function: implications for Alzheimer's disease therapy. Curr Neuropharmacol 2006; 4: 149-163
86. Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature 2006; 440: 352-357
87. Puzzo D, Privitera L, Leznik E, Fà M, Staniszewski A, Palmeri A, et al. Picomolar amyloid-β positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 2008; 28: 14537-14545
88. Parameshwaran K, Sims C, Kanju P, Vaithianathan T, Shonesy BC, Dhanasekaran M, et al. Amyloid β-peptide Aβ(1-42) but not Aβ(1-40) attenuates synaptic AMPA receptor function. Synapse 2007; 61: 367-374
89. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, et al. Regulation of NMDA receptor trafficking by amyloid-β. Nat Neurosci 2005; 8: 1051-1058
90. Parameshwaran K, Dhanasekaran M, Suppiramaniam V. Amyloid β peptides and glutamatergic synaptic dysregulation. Exp Neurol 2008; 210: 7-13.
91. Tyszkiewicz JP, Yan Z. β-Amyloid peptides impair PKC-dependent functions of metabotropic glutamate receptors in prefrontal cortical neurons. J Neurophysiol 2005; 93: 3102-3111
92. Kabogo D, Rauw G, Amritraj A, Baker G, Kar S. β-Amyloid-related peptides potentiate K+-evoked glutamate release from adult rat hippocampal slices Neurobiol Aging 2008, doi:10.1016/j.neurobiolaging.2008.08.009.
93. Griffith LC. Regulation of calcium/calmodulin-dependent protein kinase II activation by intramolecular and intermolecular interactions. J Neurosci 2004; 24: 8394-8398
94. Lisman J, Schulman H, Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 2002; 3: 175-190
95. Tardito D, Gennarelli M, Musazzi L, Gesuete R, Chiarini S, Barbiero VS, et al. Long-term soluble Aβ1-40 activates CaM kinase II in organotypic hippocampal cultures. Neurobiol Aging 2007; 28: 1388-1395
96. Cuello AC, Canneva F. Impact of intracellular β-amyloid in transgenic animals and cell models. Neurodegener Dis 2008; 5: 146-148
97. Bobich JA, Zheng Q, Campbell A. Incubation of nerve endings with a physiological concentration of Aβ 1-42 activates CaV2.2(NType)-voltage operated calcium channels and acutely increases glutamate and noradrenaline release. J Alzheimers Dis 2004; 6: 243-255
98. Trabace L, Kendrick KM, Castrignanò S, Colaianna M, De Giorgi A, Schiavone S, et al. Soluble amyloid β1-42 reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide. Neuroscience 2007; 147: 652-663
99. Wu J, Khan GM, Nichols RA. Dopamine release in prefrontal cortex in response to β-amyloid activation of α7 * nicotinic receptors. Brain Res 2007; 1182: 82-89
100. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976; 2: 1403.
101. Kar S, Slowikowski SP, Westaway D, Mount HT. Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer's disease. J Psychiatry Neurosci 2004; 29: 427-441
102. Kar S, Seto D, Gaudreau P, Quirion R. β-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal slices. J Neurosci 1996; 16: 1034-1040
103. Abe E, Casamenti F, Giovannelli L, Scali C, Pepeu G. Administration of amyloid β-peptides into the medial septum of rats decreases acetylcholine release from hippocampus in vivo. Brain Res 1994; 636: 162-164
104. Phillips AG, Vacca G, Ahn S. A top-down perspective on dopamine, motivation and memory. Pharmacol Biochem Behav 2008; 90: 236-249
105. Battaini F, Pascale A, Lucchi L, Pasinetti GM, Govoni S. Protein kinase C anchoring deficit in postmortem brains of Alzheimer's disease patients. Exp Neurol 1999; 159: 559-564
106. Cole G, Dobkins KR, Hansen LA, Terry RD, Saitoh T. Decreased levels of protein kinase C in Alzheimer brain. Brain Res 1988; 452: 165-174
107. Govoni S, Bergamaschi S, Racchi M, Battaini F, Binetti G, Bianchetti A, et al. Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients. Neurology 1993; 43: 2581-2586
108. Drachman DA. Rethinking Alzheimer's disease: the role of age-related changes. Curr Neurol Neurosci Rep 2007; 7: 265-268
109. Jiang CH, Tsien JZ, Schultz PG, Hu Y. The effects of aging on gene expression in the hypothalamus and cortex of mice. Proc Natl Acad Sci USA 2001; 98: 1930-1934
110. Selkoe DJ. Clearing the brain's amyloid cobwebs. Neuron 2001; 32: 177-180
111. Caccamo A, Oddo S, Sugarman MC, Akbari Y, La Ferla FM. Age- and region-dependent alterations in Aβ-degrading enzymes: implications for Aβ-induced disorders. Neurobiol Aging 2005; 26: 645-654
112. Wang DS, Iwata N, Hama E, Saido TC, Dickson DW. Oxidized neprilysin in aging and Alzheimer's disease brains. Biochem Biophys Res Commun 2003; 310: 236-241
113. LeBlanc A, Liu H, Goodyer C, Bergeron C, Hammond J. Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. J Biol Chem 1999; 274: 23426-23436
114. Haroutunian V, Perl DP, Purohit DP, Marin D, Khan K, Lantz M, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 1998; 55: 1185-1191
115. Thal DR, Griffin WS, Braak H. Parenchymal and vascular Aβ-deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease. J Cell Mol Med 2008; 12: 1848-1862
116. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 1997; 18: 351-357
117. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008; 65: 1509-1517
118. Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain 2007; 130: 2837-2844
119. Piccini A, Russo C, Gliozzi A, Relini A, Vitali A, Borghi R, et al. β-amyloid is different in normal aging and in Alzheimer disease. J Biol Chem 2005; 280: 34186-34192
120. Iacono D, Markesbery WR, Gross M, Pletnikova O, Rudow G, Zandi P, et al. The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life. Neurology 2009; 73: 665-673
121. Scheinin NM, Aalto S, Koikkalainen J, Lötjönen J, Karrasch M, Kemppainen N, et al. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology 2009; 73(15): 1186-1192
122. Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 2009; 66: 300-305
123. Pistoia F, Desideri G, Sarà M, Ferri C. No country for old men: a polypill strategy to prevent dementia. Eur J Neurol 2009; 16: e11.
124. Everitt BJ, Robbins TW. Central cholinergic systems and cognition. Annu Rev Psychol 1997; 48: 649-684
125. Mapstone M, Steffenella TM, Duffy CJ. A visuospatial variant of mild cognitive impairment: getting lost between aging and AD. Neurology 2003; 60: 802-808
126. McKinney M, Jacksonville MC. Brain cholinergic vulnerability: relevance to behavior and disease. Biochem Pharmacol 2005; 70: 1115-1124 (Pubitemid 41317506)
127. Ganguly R, Guha D. Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera. Indian J Med Res 2008; 128: 744-751
128. Gsell W, Jungkunz G, Riederer P. Functional neurochemistry of Alzheimer's disease. Curr Pharm Des 2004; 10: 265-293
129. Bekkers JM, Steven CF. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature 1989; 341: 230-233
130. Govoni S. Monoamines. Encyclopedia of Neuroscience. UK: Oxford Academic Press 2009; vol.5: pp. 931-937.