Alzheimer's disease: Current status of etiopathogenesis and therapeutic strategies

Pakistan Journal of Biological Sciences

Volumn 14, Issue 4, 2011, Pages 257-272

  Khairallah, Mervat Ibrahim ^a   Kassem, Lobna Abdel Aal ^a  

^a German University in Cairo   (Egypt)

Author keywords

AD therapies; Pathogenic events; Pathologies characterize; Risk factors

Indexed keywords

ANTIINFLAMMATORY AGENT; CHOLINESTERASE INHIBITOR; ENZYME INHIBITOR; METAL; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; SECRETASE; TAU PROTEIN;

AGED; ALZHEIMER DISEASE; AMYLOID PLAQUE; ARTICLE; DRUG ANTAGONISM; DRUG EFFECT; GENETICS; HOMEOSTASIS; HUMAN; MEMORY DISORDER; MENTAL DISEASE; METABOLISM; MITOCHONDRION; NERVE CELL; NEUROFIBRILLARY TANGLE; PATHOLOGY; PHYSIOLOGY;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; ANTI-INFLAMMATORY AGENTS; CHOLINESTERASE INHIBITORS; ENZYME INHIBITORS; HOMEOSTASIS; HUMANS; MEMORY DISORDERS; MENTAL DISORDERS; METALS; MITOCHONDRIA; NEUROFIBRILLARY TANGLES; NEURONS; PLAQUE, AMYLOID; RECEPTORS, N-METHYL-D-ASPARTATE; TAU PROTEINS;

EID: 79957551737     PISSN: 10288880     EISSN: 18125735     Source Type: Journal    
DOI: 10.3923/pjbs.2011.257.272     Document Type: Article

References (147)

1. Adlard, P.A. and A.I. Bush, 2006. Metals and Alzheimer's disease. J. Alzheimers. Dis., 10: 145-163.
2. Aisen, P.S., K.A. Schafer, M. Grundman, E. Pfeiffer and M. Sanoxet-Al. et-al, 2003. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: A randomized controlled trial. J. Am. Med. Assoc., 289: 2819-2826.
3. Aisen, P.S., D. Saumier, R. Briand, J. Laurin, F. Gervais, P. Tremblay and D. Garceau, 2006. A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurol., 67: 1757-1763.
4. Atwood, C.S., G. Perry, H. Zeng, Y. Kato and W.D. Jonesx, 2004. Copper mediates dityrosine cross-linking of Alzheimer's amyloid-B. Biochemistry, 43: 560-568.
5. Barnham, K.J., C.L. Masters and A.I. Bush, 2004. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov., 3: 205-214.
6. Belli, C. and B. Moosmann, 2002. Antioxidant neuroprotection in Alzheimers disease as preventive and therapeutic approach. Free Radic. Biol. Med., 33: 182-191.
7. Benard, G., N. Bellance, D. James, P. Parrone, H. Fernandez, T. Letellier and R. Rossignol, 2007. Mitochondrial bioenergetics and structural network organization. J. Cell. Sci., 120: 838-848.
8. Benardi, P., A. Krauskopf, E. Basso, V. Petronilli, E. Blalahy-Dysan, F. Di Lisa and M.A. Forte, 2006. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J., 273: 2077-2099.
9. Biran, Y., C.L. Masters, K.J. Barnham, A.I. Bush and P.A. Adlard, 2009. Pharmacotherapeutic targets in Alzheimers disease. J. CellMol. Med., 13: 61-86.
10. Bjorkdahl, C, M.J. Sjogren, B. Wmblad and J.J. Pei, 2005. Zinc induces neurofilament phosphorylation independent of p70 S6 kinase in N2a cells. Neuroreport, 16: 591-595.
11. Bulic, B., M. Pickhart, I. Khlistunova, J. Biernat, E.M. Mandelkow, E. Mandelkow and H. Waldmann, 2007. Rhodanine-based tau aggregation inhibitors in cell models of tauopathy. Angew. Chem. Int. Ed., 46: 9215-9219.
12. Bush, A.I. and R.E. Tanzi, 2008. Therapeutics for Alzheimers disease based on the metal hypothesis. Neurotherapeutics, 5: 421-432.
13. Bush, A.I., 2000. Metals and neuroscience. Curr. Opin. Chem. Biol., 4: 184-191.
14. Bush, A.I., 2002. Metal complexing agents as therapies for Alzheimers disease. Neurobiol. Aging, 23: 1031-1038.
15. Bush, A.I., 2003. The metallobiology of Alzheimers disease. Trends Neurosci., 26: 207-214.
16. Butterfield, D.A., M. Perlmgi and R. Sultana, 2006. Oxidative stress in Alzheimers disease brain: New insights from redox proteomics. Eur. J. Pharmacol., 545: 39-50.
17. Buttini, M., E. Masliah, R. Barbour, H. Grajeda and R. Motter et al, 2005. B-Amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimers disease. J. Neurosci., 25: 9096-9101.
18. Chan, D.C., 2006. Mitochondrial fusion and fission in mammals. Annu. Rev. Cell. Dev. Biol, 22: 79-99.
19. Chen, J.X. and S.D. Yan, 2007. Amyloid-[3-mduced mitochondrial dysfunction. J. Alzheimers Dis., 12: 177-184.
20. Chen, X., D.G. Walker, A.M. Schmidt O. Arancio, L.F. Lue and S.D. Yan, 2007. RAGE: A potential target for Abeta-mediated cellular perturbation in Alzheimers disease. Curr. Mol. Med., 7: 735-742.
21. Churcher, I., 2006. Tau therapeutic strategies for the treatment of Alzheimers disease. Curr. Top. Med. Chem., 6: 579-595.
22. Ciccotosto, G.D., D. Tew, C.C. Curtain, D. Smith and D. Carrington et al., 2004. Enhanced toxicity and cellular binding of a modified amyloid B peptide with a methionine to valine substitution. J. Biol. Chem., 279: 42528-42534.
23. Coleman, P., H. Federoff and R. Kurlan, 2004. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology, 63: 1155-1162.
24. Crouch, P.J., A.R. White and A.I. Bush, 2007. The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimers disease. FEBS J., 274: 3775-3783.
25. Da Cruze Silva, E.F. and O.A. da Cruze Silva, 2003. Protein phosphorylation and APP metabolism. Neurochem. Res., 28: 1553-1561.
26. De Felice, F.G., P.T. Velasco, M.P. Lambert, K. Viola, S.J. Fernandez, S.T. Ferreira and WL. Klein, 2007. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J. Biol. Chem., 282: 11590-11601.
27. Defeudis, F.V., 2002. Bilobalide and neuroprotection. Pharmacol. Res., 46: 565-568.
28. Doody, R.S., J.C. Stevens, C. Beck, R.M. Dubinsky and J.A. Kaye et al., 2001. Practice parameter: Management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American academy of neurology. Neurology, 56: 1154-1166.
29. Du, H., L. Guo, F. Fang, D. Chen and A.A. Sosunov et al., 2008. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimers disease. Nat. Med., 14: 1097-1105.
30. El-Sayed, N.S., L.A. Kassem and O.A. Heikal, 2009. Promising therapy for Alzheimers disease targeting angiotensin converting enzyme and the cyclooxygense-2 isoform. Drug Discov. Ther., 3: 307-315.
31. Evans, P. and M.A. Persinger, 2010. Erythropoietin and mild traumatic brain injury: Neuroprotective potential and dangerous side-effects. J. Biol. Sci., 10: 739-746.
32. Evin, G., M.F. Sernee and C.L. Masters, 2006. Inhibition of gamma-secretase as a therapeutic intervention for Alzheimers disease: Prospects, limitations and strategies. CNS Drugs, 20: 351-372.
33. Fener, I., T. Gomez-Isla, B. Puig, M. Freixes, E. Ribe, E. Dalfo and J. Avila, 2005. Current advances on different kinases involved in tau phosphorylation and implications in Alzheimers disease and tauopathies. Curr. Alzheimer Res., 2: 3-18.
34. Finder, V.H. and R. Glockshuber, 2007. Amyloid-beta aggregation. Neurodegener. Dis., 4: 13-27.
35. Fisher, A., 2000. Therapeutic strategies in Alzheimers disease: Ml muscarinic agonists. Japan J. Pharmacol., 84: 101-112.
36. Fisher, A., D.M. Michaelson, R. Brandeis, R. Haring, S. Chapman and Z. Pittel. 2000. Ml muscarinic agonists as potential disease-modifying agents in Alzheimers disease: Rationale and perspectives. Ann. N. Y. Acad. Sci., 920: 315-320.
37. Galindo, M.F., I. Ikuta, X. Zhu, G. Casadesus and J. Jordan, 2010. Mitochondrial biology in Alzheimers disease pathogenesis. J. Neurochem., 114: 933-945.
38. Garai, K, B. Sahoo, S.K. Kaushalya, R. Desai and S. Marti, 2007. Zinc lowers amyloid-B toxicity by selectively precipitating aggregation intermediates. Biochemistry, 46: 10655-10663.
39. Garceau, D., C. Gurbindo and J. Laurin, 2002. Safety, tolerability and pharmacokinetic profile of Alzhemed, An anti-amyloid agent for Alzheimer's disease, in healthy subjects. Proceedings of the 7th International Geneva/Spring field Symposium on Advances in Alzheimer Therapy, April 3-6, 2002, Geneva, Switzerland.
40. Geerts, H., 2004. NC-531 Neurochem. Curr. Opin. Investig. Drugs, 5: 95-100.
41. Gervais, F., R. Chalifour, D. Garceau, X. Kong and J. Laurin et al, 2001. Glycosaminoglycanmimetics: A therapeutic approach to cerebral amyloid angiopathy. Amyloid, 8: 28-35.
42. Glabe, C.G., 2008. Structural classification of toxic amyloid oligomers. J. Biol. Chem., 283: 29639-29643.
43. Glass, C.K., K. Saijo, B. Winner, M.C. Marchetto and F.H. Gage, 2010. Mechanisms underlying inflammationinneurodegeneration. Cell, 140:918-934.
44. Gogvadze, V., S. Orrenius and B. Zhivotovsky, 2006. Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim. Biophys. Acta Bioenergetics, 1757: 639-647.
45. Golde, T.E., 2003. Alzheimer disease therapy: Can the amyloid cascade be halted? J. Clin. Invest, 111: 11-18.
46. Gong, Y., L. Chang, K.L. Viola, P.N. Lacor and M.P. Lambert et al, 2003. Alzheimers disease-affected brain: presence of oligomeric AB ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl. Acad. Sci. USA., 100: 10417-10422.
47. Gu, Q.B., J.X. Zhao, J. Fei and W. Schwarz, 2004. Modulation of Na(+),K(+) pumping and neurotransmitter uptake by beta-amyloid. Neuroscience, 126: 61-67.
48. Haass, C. and DJ. Selkoe, 2007. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimers amyloid B-peptide. Nat. Rev. Mol. Cell. Biol, 8: 101-112.
49. Halestrap, A.P., G.P. McStay and S.J. Clarke, 2002. The permeability transition pore complex: Another view. Biochimie, 84: 153-166.
50. Hauptmann, S., I. Scherping, S. Drose, U. Brandt and W.E. Mullerx et-al, 2009. Mitochondrial dysfunction: An early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol. Aging, 30: 1574-1586.
51. Hemzen, E.L., A.C. Need, K.M. Hayden, O. Chiba-Falek and A.D. Roses et al, 2010. Genome-wide scan of copy number variation in late-onset Alzheimers disease. J. Alzheimers. Dis., 19: 69-77.
52. Heneka, M.T., M. Sastre, L. Dumitrescu-Ozimek, A. Hanke and I. Dewachter et al, 2005. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abetal-42 levels in APPV7171 transgenic mice. Brain, 128: 1442-1453.
53. Herrup, K., 2010. Reimagining Alzheimer's disease-An age-based hypothesis. J. Neurosci., 30: 16755-16762.
54. Hirai, K., G. Aliev, A. Nunomura, H. Fujioka and R.L Russell et al., 2001. Mitochondrial abnormalities in Alzheimers disease. J. Neurosci., 21: 3017-3023.
55. Hollenbeck, P.J., 2005. Mitochondria and neurotransmission: Evacuating the synapse. Neuron, 47: 331-333.
56. Holmes, C, D. Boche, D. Wilkinson, G. Yadegarfar and V. Hopkinsx et-al, 2008. Long-term effects of Abeta42 immunisation in Alzheimers disease: Follow- up of a randomised, placebo-controlled phase I trial. Lancet, 372: 216-223.
57. Jacobsen, J.S., P. Reinhart and M.N. Pangalos, 2005. Current concepts in therapeutic strategies targeting cognitive decline and disease modification in Alzheimers disease. NeuroRx., 2: 612-626.
58. Jick. H., G.L. Zornberg, S.S. Jick, S. Seshardi and D.A. Drachman, 2000. Statins and the risk of dementia. Lancet, 356: 1627-1631.
59. Kann, O. and R. Kovacs, 2007. Mitochondria and neuronal activity. Am. J. Physiol. Cell. Physiol., 292: C641-C657.
60. Kar, S., S.P. Slowikowski, D. Westaway and H.T. Mount, 2004. Interactions between B-amyloid and central cholinergic neurons: Implications for Alzheimers disease. J. Psychiatry Neurosci., 29: 427-441.
61. Kassem, L.A. and N.A. Yassin, 2010. Role of erythropoietin in prevention of chemotherapy-induced peripheral neuropathy. Pak. J. Biol. Sci., 13: 577-587.
62. Klafki, H.W., M. Staufenbiel, J. Kornhuber and J. Wiltfang, 2006. Therapeutic approaches to Alzheimers disease. Brain, 129: 2840-2855.
63. Klein, W.L., 2006. Cytotoxic Intermediates in the Fibrillation Pathway: A3 Oligomers in Alzheimers Disease as a Case Study. In: Protein Misfolding, Aggregation and Conformational Diseases, Uvertsky, V.N. and A.L. Fink (Eds.). Springer, New York, pp: 61-75.
64. Lacor, P.N., M.C. Buniel, L. Chang, S. Fernandez and Y. Gong et al., 2004. Synaptic targeting by Alzheimers-related amyloid beta oligomers. J. Neurosci., 24: 10191-10200.
65. Lambert, M.P., P.T. Velasco, L. Chang, K.L. Viola and S. Fernandezx et-al, 2007. Monoclonal antibodies that target pathological assemblies of Abeta. J. Neurochem., 100: 23-35.
66. Lau, T.L., E.E. Ambroggio, D.J. Tew, R. Cappai and C.L. Masters et al, 2006. Amyloid-[3 peptide disruption of lipid membranes and the effect of metal ions. J. Mol. Biol, 356: 759-770.
67. Lesne, S., M.T. Koh, L. Kotilinek, R. Kayed and C.G. Glabe et al, 2006. A specific amyloid-B protein assembly in the brain impairs memory. Nature, 440: 352-357.
68. Li, H. and X. Shen, 2000. Selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice. Chm. Med. J., 113: 1040-1042.
69. Lim, G.P., F. Yang, T. Chu, P. Chen and W. Beech et al, 2000. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimers disease. J. Neurosci., 20: 5709-5714.
70. Lindsay, J., D. Laurin, R. Veneault, R. Hebert, B. Helliwell, G. Hill and L. McDowel, 2002. Risk factors for alzheimers disease: A prospective analysis from the Canadian study of health and aging. Am. J. Epidemiol, 156: 445-453.
71. Lombardo, J.A., E.A. Stern, M.E. McLellan, S.T. Kajdasz, G.A. Hickey, B.J. Bacskai and B.T. Hyman, 2003. Amyloid-beta antibody treatment leads to rapid normalization of plaque induced neuritic alterations. J. Neurosci., 23: 10879-10883.
72. Luo, Y., B. Bolon, M.A. Damore, D. Fitzpatrick and H. Liu. et al, 2003. BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol. Dis., 14: 81-88.
73. Ma, Q., Y. Li, J. Du, K. Kanazawa, T. Nemoto, H. Nakanishi and Y. Zhao, 2005. Binding of copper (II) ion to an Alzheimer's tau peptide as revealed by MALDI-TOF MS, CD and NMR. Biopolymers, 79: 74-85.
74. Malek, M., S. Zahedi Asl, A. Sarkaki, Y. Farbood and A.H. Doulah, 2009. The effect of intra-hippocampal injection of growth hormone on spatial learning and memory in animal model of alzheimers disease. Pak. J. Biol. Sci., 12: 1237-1245.
75. Malm, T.M., H. Livonen, G. Goldsteins, V. Keksa-Goldsteine, T. Ahtonleml et al, 2007. Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting3-amyloid burden. J. Neurosci., 27: 3712-3721.
76. Massaad, C.A., T.M. Washington, R.G. Pautler and E. Klann, 2009. Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimers disease. Proc.Natl. Acad. Sci. U.S.A., 106: 13576-13581.
77. McCoy, M.K. and M.G. Tansey, 2008. TNF signaling inhibition in the CNS: Implications for normal brain function and neurodegenerative disease. J. Neuroinflammation., 2: 45-45.
78. Meraz-Rios, M.A., K.I. Lira-De Leon, V. Campos-Pena, M.A. De Anda-Hernandez and R. Mena-Lopez, 2010. Tau oligomers and aggregation in Alzheimers disease. J. Neurochem., 112: 1353-1367.
79. Metcalfe, M.J. and M.E. Figueiredo-Pereira, 2010. Relationship between tau pathology and neuroinflammation in Alzheimers disease. Mt. Sinai. J. Med., 77: 50-58.
80. Migliore, L. and F. Coppede, 2009. Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat. Res., 667: 82-97.
81. Mocellin, S., 2006. Tumor vasculature: The achilles heel of cancer. Int. J. Cancer Res., 2: 176-187.
82. Moreira, PL, M.S. Santos, A. Moreno and C. Oliveira, 2001. Amyloid beta-peptide promotes permeability transition pore in brain mitochondria. Biosci. Rep., 21: 789-800.
83. Moreira, P.I., M.S. Santos, A. Moreno, A.C. Rego and C. Oliveira, 2002. Effect of amyloid beta-peptide on permeability transition pore: A comparative study. J. Neurosci. Res., 69: 257-267.
84. Morgan, D., D.M. Diamond, P.E. Gottschall, K.E. Ugen and C. Dickey et al, 2000. A B peptide vaccination prevents memory loss in an animal model of Alzheimers disease. Nature, 408: 982-985.
85. Neugroschl, J. and M. Sano, 2010. Current treatment and recent clinical research in Alzheimers disease. Mount. Sinai J. Med., 77: 3-16.
86. Oakley, H., S.L. Cole, S. Logan, E. Maus and P. Shao et al, 2006. Intraneuronal beta-amyloid aggregates, neurodegeneration and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: Potential factors in amyloid plaque formation. J. Neurosci., 26: 10129-10140.
87. Paola, D., C. Domenicotti, M. Nitti, A. Vitali and R. Borghi et al, 2000. Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betal andbetall PKCs inNT2 cells. Biochem. Biophys. Res. Commun, 268: 642-646.
88. Pedrini, S., T.L. Carter, G. Prendergast, S. Petanceska, M.E. Ehrlich and S. Gandy, 2005. Modulation of statin-activated shedding of Alzheimer APP ectodomainby ROCK. PLoS. Med., 2: el8-el8.
89. Perry, V.H., C. Qinningham and C. Holmes, 2007. Systemic infections and inflammation affect chronic neurodegeneration. Nat. Rev. Immunol., 7: 161-167.
90. Pickhart, M., G. Larbig, I. Khlistunova, A. Coksezen and B. Meyer et al, 2007. Phenylthiazolyl-hydrazide and its derivates are potent inhibitors of Tau aggregation and toxicity in vitro and in cells. Biochemistry, 46: 10016-10023.
91. Picklo, Sr. M.J. and T.J. Montine, 2007. Mitochondrial effects of lipid-derived neurotoxins. J. Alzheimers Dis., 12: 185-193.
92. Pleckaityte, M., 2010. Alzheimers disease: A molecular mechanism, new hypotheses and therapeutic strategies. Med. (Kaunas), 46: 70-76.
93. Reisberg, B., R. Doody, A. Stoffler, F. Schmitt, S. Ferris and H.J. Mobius, 2003. Memantine in moderate- to-severe Alzheimers disease. N. Engl. J. Med., 348: 1333-1341.
94. Rogawski, M.A. and G.L. Wenk, 2003. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev., 9: 275-308.
95. 2+ dependent mechanisms of presynaptic control at central synapses. Neuroscientist, 12: 317-326.
96. Saijo, K., B. Winner, C.T. Carson, J.G. Collier and L. Boyer et al, 2009. Nurrl/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation induced death. Cell, 137: 47-59.
97. Salloway, S. and S. Correia, 2009. Alzheimer disease: Time to improve its diagnosis and treatment. Cleve. Clin. J. Med., 76: 49-58.
98. Sanchez-Ramos, J., S. Song, C. Cao and G. Arendash, 2008. The potential of hematopoietic growth factors for treatment of Alzheimers disease: A mini-review. BMC Neurosci., 9: S3-S3.
99. Sarkaki, A., R. Amani, M. Badavi, A.Z. Moghaddam, H. Aligholi, M. Safahani and M.H. Haghighizadeh, 2008. Pre-treatment effect of different doses of soy isoflavones on spatial learning and memory in an ovariectomized animal model of alzheimer s disease. Pak. J. Biol. Sci., 11: 1114-1119.
100. Sasaki, N., S. Toki, H. Chowei, T. Saito and N. Nakano et al, 2001. Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimers disease. Brain Res., 888: 256-262.
101. Sastre, M., J. Walter and S.M. Gentleman, 2008. Interactions between APP secretases and inflammatory mediators. J. Neuroinflammation, 5: 25-25.
102. Saunders, A.M., 2001. Gene identification in Alzheimer's disease. Pharmacogenomics, 2: 239-249.
103. Saura, C.A., S.Y. Choi, V. Beglopoulos, S. Malkani and D. Zhang et al, 2004. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron, 42: 23-36.
104. Sayre, L.M., G. Perry, P.L.R. Harris, Y. Liu, K.A. Schubert and M.A. Smith, 2000. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease a central role for bound transition metals. J. Neurochem., 74: 270-279.
105. Schaeffer, E.L., B.A. Novaes, E.R. da Silva, H.D. Skaf and A.G. Mendes-Neto, 2009. Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain. Prog. Neuropsychopharmacol. Biol. Psychiatry, 33: 1087-1102.
106. Schneider, L.S., S.T. DeKosky, M.R. Farlow, P.N. Tariot, R. Hoerr and M. Kieser, 2005. A randomized, double-blind, placebo-controlled trial of two doses of ginkgo biloba extract in dementia of the Alzheimers type. Curr. Alzheimer. Res., 2: 541-551.
107. Schneider, L.S., P.N. Tariot, K.S. Dagerman, S.M. Davi and J.K. Hsiao et al, 2006. Effectiveness of atypical antipsychotic drugs in patients with Alzheimers disease. N. Engl. J. Med., 355: 1525-1538.
108. Selkoe, D.J., 2001. Alzheimers disease: Genes, proteins and therapy. Physiol. Rev., 81: 741-766.
109. Serrano, F. and E. Klann, 2004. Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res. Rev., 3: 431-443.
110. Shishodia, S., G. Sethi and B.B. Aggarwal, 2005. Curcumin: Getting back to the roots. Ann. N. Y. Acad. Sci., 1056: 206-217.
111. Silvestrelli, G., A. Lanari, L. Parnetti, D. Tomassoni and F. Amenta, 2006. Treatment of Alzheimers disease: From pharmacology to a better understanding of disease pathophysiology. Mech. Ageing. Dev., 127: 148-157.
112. Simi, A., N. Tsakin, P. Wang and NJ. Rothwell, 2007. Interleukin-1 and inflammatory neurodegeneration. Biochem. Soc. Trans., 35: 1122-1126.
113. Siren, A.L., T. Fasshauer, C. Bartels and H. Ehrenreich, 2009. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics, 6: 108-127.
114. Smith, P.J., J.A. Blumenthal, M.A. Babyak, L. Craighead and K.A. Welsh-Bohmer et al, 2010. Effects of the dietary approaches to stop hypertension diet, exercise and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension, 55: 1331-1338.
115. Sonkusare, S.K., C.L. Kaul and P. Ramarao, 2005. Dementia of Alzheimers disease and other neurodegenerative disorders- memantine, a new hope. Pharmacol. Res., 51: 1-17.
116. Stoothoff, W.H. and G.V.W. Johnson, 2005. Tau phosphorylation: Physiological and pathological consequences. Biochim. Biophys. Acta., 1739: 280-297.
117. Suh, S.W., K.B. Jensen, M.S. Jensen, D.S. Suva, P.J. Kesslak, G. Danscher and C.J. Frederickson, 2000. Histochemically-reactive zinc in amyloid plaques, angiopathy and degenerating neurons of Alzheimers diseased brains. Brain Res., 852: 274-278.
118. Sun, X., S. Sato, O. Murayama, M. Murayama, J.M. Park, H. Yamaguchi and A. Takashima, 2002. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein CI 00. Neurosci. Lett, 321: 61-64.
119. Szekely, C.A., J.E. Thorne, P.P. Zandi, M. Ek, E. Messias, J.C. Breitner and S.N. Goodman, 2004. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimers disease: A systematic review. Neuroepidemiology, 23: 159-169.
120. Tamagno, E., M. Guglielmotto, M. Aragno, R. Borghi and R. Autelli et al., 2008. Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein. J. Neurochem., 104: 683-695.
121. Tariot, P.N., M.R. Farlow, G.T. Grossberg, S.M. Graham, S. McDonald, I. Gergel and Memantine Study Group, 2004. Memantine treatment in patients with moderate to severe Alzheimers disease already receiving donepezil. A randomized controlled trial. JAMA., 291: 317-324.
122. Trmh, N.H., J. Hoblyn, S. Mohanty and K. Yaffe, 2003. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: A meta-analysis. J. Am. Med. Assco., 289: 210-216.
123. Tschape, J.A. and T. Hartmann, 2006. Therapeutic perspectives in Alzheimers disease. Recent Patents. CNSDrugDiscov., 1: 119-127.
124. Tuppo, E.E. and H.R. Arias, 2005. The role of inflammation in Alzheimers disease. Cell. Biol, 37: 289-305.
125. Tyas, S.L., J. Manfreda, L.A. Strain and P.R. Montgomery, 2001. Risk factors for Alzheimers disease: A population-based, longitudinal study in Manitoba, Canada. Int. J. Epidemiol., 30: 590-597.
126. Van Den Heuvel, C, E. Thornton and R. Vink, 2007. Traumatic brain injury and Alzheimers disease: A review. Prog. Brain Res., 161: 303-316.
127. Vetrivel, K.S., Y.W. Zhang, H. Xu and G. Thinakaran, 2006. Pathological and physiological functions of presenilins. Mol. Neurodegener., 1: 4-4.
128. Vlassara, H., W. Cai, J. Crandall, T. Goldberg and R. Oberstein et al., 2002. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc. Natl. Acad. Sci. USA., 99: 15596-15601.
129. Wakabayashi, T. and B. De Strooper, 2008. Presenilins: Members of the?-secretase quartets, but part-time soloists too. Physiology, 23: 194-204.
130. Walker, L.C., C.C. Ibegbu, C.W. Todd, H.L. Robinson, M. Jucker, H. LeVine and S. Gandy, 2005. Emerging prospects for the disease-modifying treatment of Alzheimers disease. Biochem. Pharmacol., 69: 1001-1008.
131. Wallace, D.C., 2005. A mitochondrial paradigm of metabolic and degenerative diseases, aging and cancer: A dawn for evolutionary medicine. Annu. Rev. Genet., 39: 359-407.
132. Walsh, D.M. and D.J. Selkoe, 2007. A3 oligomers-a decade of discovery. J. Neurochem., 101: 1172-1184.
133. Wang, Y., S.L. Chan, L. Miele, P.J. Yao, J. Mackes, D.K. Ingram, M.P. Mattson and K. Furukawa, 2004. Involvement of Notch signaling in hippocampal synaptic plasticity. Proc. Natl. Acad. Sci., 101: 9458-9462.
134. Wang, X., B. Su, H. Fujioka and X. Zhu, 2008. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimers disease patients. Am. J. Pathol, 173: 470-482.
135. Weggen, S., J.L. Eriksen, P. Das, S.A. Sagi and R. Wang et al, 2001. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature, 414: 212-216.
136. White, A.R., T. Du, K.M. Laughton, I. Volitakis and R.A. Sharpies et al, 2006. Degradation of the Alzheimer disease amyloid beta peptide by metal dependent up-regulation of metalloprotease activity. J. Biol. Chem., 281: 17670-17680.
137. Wolf, B.A., A.M. Wertkm, Y.C. Jolly, R.P. Yasuda and B.B. Wolfe et al, 1995. Muscarinic regulation of Alzheimers disease amyloid precursor protein secretion and amyloid beta- protein production in human neuronal NT2N cells. J. Biol. Chem., 270: 4916-4922.
138. Wolozin, B., W. Kellman, P. Ruosseau, G.G. Celesia and G. Siegel, 2000. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arch. Neurol, 57: 1439-1443.
139. Wu, Q.Y., J. Li, Z.T. Feng and T.H. Wang, 2007. Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimers disease rat model. Neurosci. Lett., 471: 281-285.
140. Yaari, R. and J. Corey-Bloom, 2007. Alzheimers disease: Pathology and pathophysiology. Semin. Neurol, 27: 32-41.
141. Yang, F., G.P. Lim, A.N. Begum, O.J. Ubeda, M.R. Simmons et al, 2005. Curcumin inhibits formation of amyloid [3 oligomers and fibrils, binds plaques and reduces amyloid in vivo. J. Biol. Chem., 280: 5892-5901.
142. Yoshiike, Y., K. Tanemura, O. Murayama, T. Akagi and M. Murayama et al, 2001. New insights on how metals disrupt amyloid aggregation and their effects on amyloid-p cytotoxicity. J. Biol. Chem., 276: 32293-32299.
143. Zaciragic, A., O. Lepara, A. Valjevac, S. Arslanagic and A. Fajkic et al, 2007. Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimers disease. J. Alzheimers. Dis., 12: 151-156.
144. Zamzami, N., N. Larochette and G. Kroemer, 2005. Mitochondrial permeability transition in apoptosis andnecrosis. Cell Death Differ., 12: 1478-1480.
145. Zandi, P.P., J.C. Anthony, A.S. Khachaturian, S.V. Stone and D. Gustafson et al., 2004. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The cache county study. Arch. Neurol., 61: 82-88.
146. Zatta, P., G. Tognon and P. Carampin, 2003. Melatonin prevents free radical formation due to the interaction between [3-amyloid peptides and metal ions [Al(III), Zn(II), Cu(II) Mn(II), Fe(H)]. J. Pineal. Res., 35: 98-103.
147. Zhou, L.X., J.T. Du, Z.Y. Zeng, W.H. Wu and Y.F. Zhao etal., 2007. Copper (II) modulates in vitro aggregation of a tau peptide. Peptides, 28: 2229-2234.