Molecular pathogenesis of alzheimer’s disease: An update

Annals of Neurosciences

Volumn 24, Issue 1, 2017, Pages 46-54

  Sanabria Castro, Alfredo ^a   Alvarado Echeverría, Ileana ^a   Monge Bonilla, Cecilia ^a  

^a HOSPITAL SAN JUAN DE DIOS   (Costa Rica)

Author keywords

Alzheimer s disease; Amyloid; Dementia; Neurobiology; Pathogenesis; Review

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PROTEIN; CALCIUM; TAU PROTEIN;

AGING; ALZHEIMER DISEASE; BLOOD BRAIN BARRIER; CALCIUM HOMEOSTASIS; CELL DEATH; CELL SURVIVAL; CHOLINERGIC SYSTEM; COGNITIVE DEFECT; GLUTAMATERGIC SYNAPSE; HUMAN; MOLECULAR PATHOLOGY; NERVE DEGENERATION; NEUROPATHOLOGY; NEUROTRANSMISSION; OXIDATIVE STRESS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW;

EID: 85019247005     PISSN: 09727531     EISSN: 09763260     Source Type: Journal    
DOI: 10.1159/000464422     Document Type: Review

References (105)

1. Alzheimer A: Uber einen eigenartigen schweren erkrankungsprozeβ der hirnrincle. Neurol Cent 1906; 25: 1134.
2. Terry AV Jr, 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: 821-827.
3. Schaeffer EL, Gattaz WF: Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology (Berl) 2008; 198: 1-27.
4. Watanabe S, Kato I, Koizuka I: Retrograde-labeling of pretecto-vestibular pathways in cats. Auris Nasus Larynx 2003; 30(suppl):S35-S40.
5. Liskowsky W, Schliebs R: Muscarinic acetylcholine receptor inhibition in transgenic Alzheimer- like Tg2576 mice by scopolamine favours the amyloidogenic route of processing of amyloid precursor protein. Int J Dev Neurosci 2006; 24: 149-156.
6. Li Y, Yuan X, Shen Y, Zhao J, Yue R, Liu F, et al: Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune-mediated clearance of β-amyloid. Aging (Albany NY) 2016; 8: 521-533.
7. Saraf MK, Anand A, Prabhakar S: Scopolamine induced amnesia is reversed by Bacopa monniera through participation of kinase-CREB pathway. Neurochem Res 2010; 35:279-287.
8. Saraf MK, Prabhakar S, Khanduja KL, Anand A: Bacopa monniera attenuates scopolamineinduced impairment of spatial memory in mice. Evid Based Complement Alternat Med 2011; 2011: 236186.
9. Caccamo A, Oddo S, Billings LM, Green KN, Martinez-Coria H, Fisher A, et al: M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 2006; 49: 671-682.
10. Fisher A: M1 muscarinic agonists target major hallmarks of Alzheimer’s disease - an update. Curr Alzheimer Res 2007; 4: 577-580.
11. Fisher A, Medeiros R, Barner N, Natan N, Brandeis R, Elkon H, et al: M1 muscarinic agonists and a multipotent activator of sigma1/ M1 muscarinic receptors: future therapeutics of Alzheimer’s disease. Alzheimers Demen 2014; 10:P123.
12. Fisher A: M1 muscarinic agonists target major hallmarks of Alzheimer’s disease - the pivotal role of brain M1 receptors. Neurodegener Dis 2008; 5: 237-240.
13. Ellis JR, Ellis KA, Bartholomeusz CF, Harrison BJ, Wesnes KA, Erskine FF, et al: Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans. Int J Neuropsychopharmacol 2006; 9: 175-189.
14. Ringman JM, Cummings JL: Current and emerging pharmacological treatment options for dementia. Behav Neurol 2006; 17: 5-16.
15. Wu J, Ishikawa M, Zhang J, Hashimoto K:Brain imaging of nicotinic receptors in Alzheimer’s disease. Int J Alzheimers Dis 2010; 2010: 548913.
16. Wenk GL: Neuropathologic changes in Alzheimer’s disease: potential targets for treatment. J Clin Psychiatry 2006; 67(suppl 3):3-7; quiz 23.
17. Mesulam M: The cholinergic lesion of Alzheimer’s disease: pivotal factor or side show? Learn Mem 2004; 11: 43-49.
18. Shen J, Wu J: Nicotinic cholinergic mechanisms in Alzheimer’s disease. Int Rev Neurobiol 2015; 124: 275-292.
19. Ni R, Marutle A, Nordberg A: Modulation of α7 nicotinic acetylcholine receptor and fibrillar amyloid-β interactions in Alzheimer’s disease brain. J Alzheimers Dis 2013; 33: 841-851.
20. Dong XX, Wang Y, Qin Z: Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin 2009; 30: 379-387.
21. Lin H, Vicini S, Hsu FC, Doshi S, Takano H, Coulter DA, et al: Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons. Proc Natl Acad Sci U S A 2010; 107: 16661-16666.
22. Geerts H, Grossberg GT: Pharmacology of acetylcholinesterase inhibitors and N-methyl-D-aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. J Clin Pharmacol 2006; 46(7 suppl 1):8S-16S.
23. Mohandas E, Rajmohan V, Raghunath B:Neurobiology of Alzheimer’s disease. Indian J Psychiatry 2009; 51: 55.
24. Lynch MA: Long-term potentiation and memory. Physiol Rev 2004; 84: 87-136.
25. Beck J, Lenart B, Kintner DB, Sun D: Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity. J Neurosci 2003; 23: 5061-5068.
26. Friedman LK: Calcium: a role for neuroprotection and sustained adaptation. Mol Interv 2006; 6: 315-329.
27. Szado T, Vanderheyden V, Parys JB, De Smedt H, Rietdorf K, Kotelevets L, et al: Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci U S A 2008; 105: 2427-2432.
28. Fan MMY, Raymond LA: N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease. Prog Neurobiol 2007; 81: 272-293.
29. Navarro A, Boveris A: The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 2007; 292:C670-C686.
30. Jung KH, Chu K, Lee ST, Park HK, Kim JH, Kang KM, et al: Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition. Biochem Biophys Res Commun 2009; 378: 507-512.
31. Ndountse LT, Chan HM: Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity. Toxicol Lett 2009; 184: 50-55.
32. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, et al: Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 2005; 8: 1051-1058.
33. Parameshwaran K, Dhanasekaran M, Suppiramaniam V: Amyloid beta peptides and glutamatergic synaptic dysregulation. Exp Neurol 2008; 210: 7-13.
34. Butterfield DA, Pocernich CB: The glutamatergic system and Alzheimer’s disease: therapeutic implications. CNS Drugs 2003; 17: 641-652.
35. Doraiswamy PM: Non-cholinergic strategies for treating and preventing Alzheimer’s disease. CNS Drugs 2002; 16: 811-824.
36. Walton HS, Dodd PR: Glutamate-glutamine cycling in Alzheimer’s disease. Neurochem Int 2007; 50: 1052-1066.
37. Pena F, Gutierrez-Lerma A, Quiroz-Baez R, Arias C: The role of beta-amyloid protein in synaptic function: implications for Alzheimer’s disease therapy. Curr Neuropharmacol 2006; 4: 149-163.
38. Doggrell SA, Evans S: Treatment of dementia with neurotransmission modulation. Expert Opin Investig Drugs 2003; 12: 1633-1654.
39. Cummings JL, Doody R, Clark C: Diseasemodifying therapies for Alzheimer disease:challenges to early intervention. Neurology 2007; 69: 1622-1634.
40. Deane R, Bell RD, Sagare A, Zlokovic BV:Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2009; 8: 16-30.
41. Jucker M, Walker LC: Neurodegeneration:amyloid-β pathology induced in humans. Nature 2015; 525: 193-194.
42. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, et al: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 2005; 47: 191-199.
43. Bertram L, Tanzi RE: Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008; 9: 768-778.
44. Wu LG, Saggau P: Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 1997; 20: 204-212.
45. Leao RN, Colom LV, Borgius L, Kiehn O, Fisahn A: Medial septal dysfunction by Aβ- induced KCNQ channel-block in glutamatergic neurons. Neurobiol Aging 2012; 33: 2046-2061.
46. De Strooper B: Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol Rev 2010; 90: 465-494.
47. Tanzi RE, Bertram L: Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 2005; 120: 545-555.
48. Lichtenthaler SF, Haass C: Amyloid at the cutting edge: activation of alpha-secretase prevents amyloidogenesis in an Alzheimer disease mouse model. J Clin Invest 2004; 113:1384-1387.
49. Sennvik K, Fastbom J, Blomberg M, Wahlund LO, Winblad B, Benedikz E: Levels of alphaand beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 2000; 278:169-172.
50. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, Palmeri A, et al: Picomolar amyloidbeta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 2008; 28: 14537-14545.
51. Velliquette RA, O’Connor T, Vassar R: Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer’s disease pathogenesis. J Neurosci 2005; 25: 10874-10883.
52. Siegel GS, Chauhan N, Karczmar AG: Links between Amyloid and Tau Biology in Alzheimer’s Disease and Their Cholinergic Aspects. Exploring the Vertebrate Central Cholinergic Nervous System. New York, 2007, pp 597-603.
53. Wen Y, Onyewuchi O, Yang S, Liu R, Simpkins JW: Increased beta-secretase activity and expression in rats following transient cerebral ischemia. Brain Res 2004; 1009: 1-8.
54. Bourne KZ, Ferrari DC, Lange-Dohna C, Rossner S, Wood TG, Perez-Polo JR: Differential regulation of BACE1 promoter activity by nuclear factor-kappaB in neurons and glia upon exposure to beta-amyloid peptides. J Neurosci Res 2007; 85: 1194-1204.
55. Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, et al: Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 2007; 282: 10873-10880.
56. De Strooper B: Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 2003; 38: 9-12.
57. Goedert M, Spillantini MG: A century of Alzheimer’s disease. Science 2006; 314: 777-781.
58. Seo SJ, Hwang DY, Cho JS, Chae KR, Kim CK, Shim SB, et al: PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production. Neurochem Res 2007; 32: 1016-1023.
59. Uemura K, Lill CM, Li X, Peters JA, Ivanov A, Fan Z, et al: Allosteric modulation of PS1/ gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS One 2009; 4:e7893.
60. Simon A, Frechilla D, del Rio J: Perspectivas sobre la hipotesis de la cascada del amiloide en la enfermedad de Alzheimer. Rev Neurol 2010; 50: 667-675.
61. Wang DS, Dickson DW, Malter JS: Beta-amyloid degradation and Alzheimer’s disease. J Biomed Biotechnol 2006; 2006: 58406.
62. Chen X, Walker DG, Schmidt AM, Arancio O, Lue LF, Yan SD: RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer’s disease. Curr Mol Med 2007; 7:735-742.
63. McGeer PL, Rogers J, McGeer EG: Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years. J Alzheimers Dis 2006; 9(3 suppl):271-276.
64. Origlia N, Righi M, Capsoni S, Cattaneo A, Fang F, Stern DM, et al: Receptor for advanced glycation end product-dependent activation of p38 mitogen-activated protein kinase contributes to amyloid-beta-mediated cortical synaptic dysfunction. J Neurosci 2008; 28: 3521-3530.
65. Aisen PS: Alzheimer’s disease therapeutic research:the path forward. Alzheimers Res Ther 2009; 1: 2.
66. Miners JS, Baig S, Tayler H, Kehoe PG, Love S: Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity. J Neuropathol Exp Neurol 2009; 68: 902-914.
67. Grbovic OM, Mathews PM, Jiang Y, Schmidt SD, Dinakar R, Summers-Terio NB, et al:Rab5-stimulated up-regulation of the endocytic pathway increases intracellular betacleaved amyloid precursor protein carboxylterminal fragment levels and Abeta production. J Biol Chem 2003; 278: 31261-31268.
68. Pasternak SH, Callahan JW, Mahuran DJ: The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer’s disease: reexamining the spatial paradox from a lysosomal perspective. J Alzheimers Dis 2004; 6: 53-65.
69. Funderburk SF, Marcellino BK, Yue Z: Cell “self-eating” (autophagy) mechanism in Alzheimer’s disease. Mt Sinai J Med 2010; 77:59-68.
70. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, et al: Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441: 880-884.
71. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al:Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441: 885-889.
72. Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, et al: Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 2008; 28: 6926-6937.
73. Rusten TE, Simonsen A: ESCRT functions in autophagy and associated disease. Cell Cycle 2008; 7: 1166-1172.
74. Nixon RA: Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci 2007; 120(pt 23):4081-4091.
75. Helmfors L, Boman A, Civitelli L, Nath S, Sandin L, Janefjord C, et al: Protective properties of lysozyme on β-amyloid pathology:Implications for Alzheimer disease. Neurobiol Dis 2015; 83: 122-133.
76. Fuentes GP, Slachevsky CA: Enfermedad de Alzheimer: actualizacion en terapia farmacologica. Rev Med Chil 2005; 133:224-230.
77. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al: Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 2007; 316: 750-754.
78. Wang HY, Li W, Benedetti NJ, Lee DH: Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced tau protein phosphorylation. J Biol Chem 2003; 278:31547-31553.
79. Zheng WH, Bastianetto S, Mennicken F, Ma W, Kar S: Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. Neuroscience 2002; 115: 201-211.
80. Gotz J, Chen F, van Dorpe J, Nitsch RM: Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001; 293: 1491-1495.
81. Stancu IC, Vasconcelos B, Terwel D, Dewachter I: Models of β-amyloid induced Taupathology:the long and “folded” road to understand the mechanism. Mol Neurodegener 2014; 9: 51.
82. Goedert M, Klug A, Crowther RA: Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis 2006; 9(3 suppl):195-207.
83. Citron M: Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov 2010; 9: 387-398.
84. Kuret J, Congdon EE, Li G, Yin H, Yu X, Zhong Q: Evaluating triggers and enhancers of tau fibrillization. Microsc Res Tech 2005; 67: 141-155.
85. Rafii MS, Aisen PS: Recent developments in Alzheimer’s disease therapeutics. BMC Med 2009; 7: 7.
86. Stoothoff WH, Johnson GV: Tau phosphorylation:physiological and pathological consequences. Biochim Biophys Acta 2005; 1739:280-297.
87. Lin MT, Beal MF: Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443: 787-795.
88. Gandhi S, Abramov AY: Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012; 2012: 428010.
89. Pratico D: Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 2008; 29: 609-615.
90. Makhaeva GF, Lushchekina S V, Boltneva NP, Sokolov VB, Grigoriev VV, Serebryakova OG, et al: Conjugates of γ-carbolines and phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer disease. Sci Rep 2015; 5: 13164.
91. Zhao Y, Zhao B: Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2013; 2013: 316523.
92. Grivennikova VG, Vinogradov AD: Generation of superoxide by the mitochondrial Complex I. Biochim Biophys Acta 2006; 1757:553-561.
93. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al: Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 2001; 21: 3017-3023.
94. Zhu X, Perry G, Moreira PI, Aliev G, Cash AD, Hirai K, et al: Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease. J Alzheimers Dis 2006; 9:147-153.
95. Korol’ TY, Korol’ SV, Kostyuk EP, Kostyuk PG: Disruption of calcium homeostasis in Alzheimer’s disease. Neurophysiology 2008; 40:385-392.
96. Magi S, Castaldo P, Macri ML, Maiolino M, Matteucci A, Bastioli G, et al: Intracellular calcium dysregulation: implications for Alzheimer’s disease. Biomed Res Int 2016; 2016:6701324.
97. Fonseca AC, Cardoso SM, Pereira CF:Calcium and redox homeostasis in Alzheimer’s disease: a focus on the endoplasmic reticulum. Ther Targets Neurol Dis 2014; 1: 1-13.
98. Stutzmann GE, Caccamo A, LaFerla FM, Parker I: Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer’s-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 2004; 24: 508-513.
99. Hagenston AM, Rudnick ND, Boone CE, Yeckel MF: 2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons. Cell Calcium 2009; 45: 310-317.
100. Small DH: Dysregulation of calcium homeostasis in Alzheimer’s disease. Neurochem Res 2009; 34: 1824-1829.
101. Wang JM, Sun C: Calcium and neurogenesis in Alzheimer’s disease. Front Neurosci 2010; 4: 194.
102. Green KN, Smith IF, Laferla FM: Role of calcium in the pathogenesis of Alzheimer’s disease and transgenic models. Subcell Biochem 2007; 45: 507-521.
103. Arispe N, Rojas E, Pollard HB: Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. Proc Natl Acad Sci U S A 1993; 90: 567-571.
104. Crompton M, Barksby E, Johnson N, Capano M: Mitochondrial intermembrane junctional complexes and their involvement in cell death. Biochimie 2002; 84: 143-152.
105. Giorgio V, Soriano ME, Basso E, Bisetto E, Lippe G, Forte MA, et al: Cyclophilin D in mitochondrial pathophysiology. Biochim Biophys Acta 2010; 1797: 1113-1118.