Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer's disease

Neuroscience Bulletin

Volumn 29, Issue 1, 2013, Pages 111-120

  Lin, Lian Feng ^a   Liao, Min Jing ^a,c   Xue, Xiao Yan ^d   Zhang, Wei ^a   Yan, Li ^a   Cai, Liang ^a   Zhou, Xiao Wen ^a   Zhou, Xing ^a   Luo, Huan Min ^a,b  

^a MEDICAL COLLEGE OF JINAN UNIVERSITY   (China)

^b JINAN UNIVERSITY   (China)

^c HUNAN NORMAL UNIVERSITY   (China)

^d Ganzhou People's Hospital   (China)

Author keywords

Alzheimer's disease; Amyloid beta; Neurotrophic factors; Treatment

Indexed keywords

ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BAPINEUZUMAB; BRAIN DERIVED NEUROTROPHIC FACTOR; FLORBETABEN; GLYCOGEN SYNTHASE KINASE 3; LITHIUM; NAPROXEN; NEUROTROPHIC FACTOR; NEUROTROPHIN RECEPTOR P75; PLACEBO; SEMAGACESTAT; TARENFLURBIL; TAU PROTEIN;

ALZHEIMER DISEASE; AMYLOID PLAQUE; DOWN REGULATION; HIPPOCAMPAL CA1 REGION; HUMAN; LONG TERM POTENTIATION; MILD COGNITIVE IMPAIRMENT; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NERVE DEGENERATION; NEUROFIBRILLARY TANGLE; NONHUMAN; PATHOGENESIS; POSITIVE FEEDBACK; POSITRON EMISSION TOMOGRAPHY; PROTEIN PHOSPHORYLATION; REVIEW; SENILE PLAQUE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; HUMANS; METABOLIC CLEARANCE RATE; NERVE GROWTH FACTORS;

EID: 84873280309     PISSN: 16737067     EISSN: 19958218     Source Type: Journal    
DOI: 10.1007/s12264-012-1287-6     Document Type: Review

References (107)

1. Lin LF, Luo HM. Screening of treatment targets for Alzheimer's disease from the molecular mechanisms of impairment by β-amyloid aggregation and tau hyperphosphorylation. Neurosci Bull 2011, 27: 53-60.
2. Holtzman DM, Morris JC, Goate AM. Alzheimer's disease: the challenge of the second century. Sci Transl Med 2011, 3: 77sr71.
3. Winslow BT, Onysko MK, Stob CM, Hazlewood KA. Treatment of Alzheimer disease. Am Fam Physician 2011, 83: 1403-1412.
4. Aisen PS, Cummings J, Schneider LS. Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer disease. Cold Spring Harb Perspect Med 2012, 2: a006395.
5. Olivares D, Deshpande VK, Shi Y, Lahiri DK, Greig NH, Rogers JT, et al. N-Methyl D-Aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease. Curr Alzheimer Res 2012, 9(6): 746-758.
6. Jo J, Whitcomb DJ, Olsen KM, Kerrigan TL, Lo SC, Bru- Mercier G, et al. Abeta(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK- 3beta. Nat Neurosci 2011, 14(5): 545-547.
7. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 2008, 14: 837-842.
8. Shipton OA, Leitz JR, Dworzak J, Acton CE, Tunbridge EM, Denk F, et al. Tau protein is required for amyloid {beta}- induced impairment of hippocampal long-term potentiation. J Neurosci 2011, 31: 1688-1692.
9. Peng S, Garzon DJ, Marchese M, Klein W, Ginsberg SD, Francis BM, et al. Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease. J Neurosci 2009, 29: 9321-9329.
10. Van Muiswinkel FL, Veerhuis R, Eikelenboom P. Amyloid beta protein primes cultured rat microglial cells for an enhanced phorbol 12-myristate 13-acetate-induced respiratory burst activity. J Neurochem 1996, 66: 2468-2476.
11. Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, et al. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci U S A 1994, 91: 3270-3274.
12. 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.
13. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol 2009, 118: 103-113.
14. Serlin Y, Levy J, Shalev H. Vascular pathology and bloodbrain barrier disruption in cognitive and psychiatric complications of type 2 diabetes mellitus. Cardiovasc Psychiatry Neurol 2011, 2011: 609202.
15. Yokel RA. Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metalinduced neurodegeneration. J Alzheimer's Dis 2006, 10: 223-253.
16. Plassman BL, Havlik RJ, Steffens DC, Helms MJ, Newman TN, Drosdick D, et al. Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 2000, 55: 1158-1166.
17. Lye TC, Shores EA. Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol Rev 2000, 10: 115-129.
18. Sotiropoulos I, Catania C, Pinto LG, Silva R, Pollerberg GE, Takashima A, et al. Stress acts cumulatively to precipitate Alzheimer's disease-like tau pathology and cognitive deficits. J Neurosci 2011, 31: 7840-7847.
19. Tran TT, Srivareerat M, Alkadhi KA. Chronic psychosocial stress accelerates impairment of long-term memory and late-phase long-term potentiation in an at-risk model of Alzheimer's disease. Hippocampus 2011, 21: 724-732.
20. Keller JN. Interplay between oxidative damage, protein synthesis, and protein degradation in Alzheimer's disease. J Biomed Biotechnol 2006, 2006: 1-3.
21. Ding QX, Dimayuga E, Keller JN. Oxidative damage, protein synthesis, and protein degradation in Alzheimer's disease. Current Alzheimer Res 2007, 4: 73-79.
22. Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, et al. A Phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol 2010, 68: 521-534.
23. Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, et al. Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study. J Neural Transmission 2011, 118: 463-471.
24. Levy YS, Gilgun-Sherki Y, Melamed E, Offen D. Therapeutic potential of neurotrophic factors in neurodegenerative diseases. BioDrugs 2005, 19: 97-127.
25. Ji C, Song C, Zuo P. The mechanism of memory impairment induced by Abeta chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus. Curr Alzheimer Res 2011, 8: 410-420.
26. Caraci F, Copani A, Nicoletti F, Drago F. Depression and Alzheimer's disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 2010, 626: 64-71.
27. Ciobica A, Padurariu M, Bild W, Stefanescu C. Cardiovascular risk factors as potential markers for mild cognitive impairment and Alzheimer's disease. Psychiatr Danub 2011, 23: 340-346.
28. Trudeau F, Gagnon S, Massicotte G. Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabetes mellitus. Eur J Pharmacol 2004, 490: 177-186.
29. Miners JS, Van Helmond Z, Chalmers K, Wilcock G, Love S, Kehoe PG. Decreased expression and activity of neprilysin in Alzheimer disease are associated with cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2006, 65: 1012-1021.
30. El-Amouri SS, Zhu H, Yu J, Marr R, Verma IM, Kindy MS. Neprilysin: An enzyme candidate to slow the progression of Alzheimer's disease. American J Pathology 2008, 172: 1342-1354.
31. Miners JS, Kehoe P, Love S. Neprilysin protects against cerebral amyloid angiopathy and Abeta-induced degeneration of cerebrovascular smooth muscle cells. Brain Pathol 2011, 21(5):594-605.
32. Nicholls DG. Mitochondrial calcium function and dysfunction in the central nervous system. Biochim Biophys Acta 2009, 1787: 1416-1424.
33. Duchen MR. Mitochondria in health and disease: perspectives on a new mitochondrial biology. Mol Aspects Med 2004, 25: 365-451.
34. Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics. J Cell Physiol 2011, 226: 2484-2493.
35. Scott HA, Gebhardt FM, Mitrovic AD, Vandenberg RJ, Dodd PR. Glutamate transporter variants reduce glutamate uptake in Alzheimer's disease. Neurobiol Aging 2011, 32: 553 e551-553 e511.
36. Guillozet-Bongaarts AL, Garcia-Sierra F, Reynolds MR, Horowitz PM, Fu YF, Wang TY, et al. Tau truncation during neurofibrillary tangle evolution in Alzheimer's disease. Neurobiol Aging 2005, 26: 1015-1022.
37. Pei JJ, Braak H, Gong CX, Grundke-Iqbal I, Iqbal K, Winblad B, et al. Up-regulation of cell division cycle (cdc) 2 kinase in neurons with early stage Alzheimer's disease neurofibrillary degeneration. Acta Neuropathol 2002, 104: 369-376.
38. Lee DC, Rizer J, Selenica ML, Reid P, Kraft C, Johnson A, et al. LPS-induced inflammation exacerbates phospho-tau pathology in rTg4510 mice. J Neuroinflammation 2010, 7: 56.
39. Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC, Wegiel J. Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease. Neurobiol Aging 2004, 25: 663-674.
40. Griffin R, Nally R, Nolan Y, McCartney Y, Linden J, Lynch MA. The age-related attenuation in long-term potentiation is associated with microglial activation. J Neurochem 2006, 99: 1263-1272.
41. Farfara D, Lifshitz V, Frenkel D. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. J Cell Mol Med 2008, 12: 762-780.
42. Ha C, Ryu J, Park CB. Metal ions differentially influence the aggregation and deposition of Alzheimer's beta-amyloid on a solid template. Biochemistry 2007, 46: 6118-6125.
43. Zatta P, Drago D, Bolognin S, Sensi SL. Alzheimer's disease, metal ions and metal homeostatic therapy. Trends Pharmacol Sci 2009, 30: 346-355.
44. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, et al. 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 2006, 26: 10129-10140.
45. Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, et al. Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Neurology 2003, 60: 235-239.
46. Leoni V. The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease. Clin Chem Lab Med 2011, 49: 375-383.
47. Hardy J, Orr H. The genetics of neurodegenerative diseases. J Neurochem 2006, 97: 1690-1699.
48. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 2006, 38: 24-26.
49. Barthel H, Luthardt J, Becker G, Patt M, Hammerstein E, Hartwig K, et al. Individualized quantification of brain betaamyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer's disease and healthy controls. Eur J Nucl Med Mol Imaging 2011, 38: 1702-1714.
50. Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol 2011, 10: 424-435.
51. Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ. Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci U S A 2011, 108: 5819-5824.
52. Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates β-amyloid- induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology 2010, 59: 542-550.
53. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and proinflammatory signaling. J Neurosci Res 2002, 70: 462-473.
54. Garzon D, Yu G, Fahnestock M. A new brain-derived neurotrophic factor transcript and decrease in brain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex. J Neurochem 2002, 82: 1058-1064.
55. Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brainderived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 2005, 93: 1412-1421.
56. Selkoe DJ. Alzheimer's disease. Cold Spring Harb Perspect Biol 2011: Epub.
57. Seeman P, Seeman N. Alzheimer's disease: beta-amyloid plaque formation in human brain. Synapse 2011, 65(12): 1289-1297.
58. Ohyagi Y. Intracellular amyloid beta-protein as a therapeutic target for treating Alzheimer's disease. Curr Alzheimer Res 2008, 5: 555-561.
59. Roberson ED, Mucke L. 100 years and counting: prospects for defeating Alzheimer's disease. Science 2006, 314: 781-784.
60. West MJ, Coleman PD, Flood DG, Troncoso JC. Differ ences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet 1994, 344: 769-772.
61. Bobinski M, Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de Leon MJ, et al. Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol 1997, 56: 414-420.
62. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr, et al. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology 2001, 56: 127-129.
63. Capsoni S, Giannotta S, Cattaneo A. Beta-amyloid plaques in a model for sporadic Alzheimer's disease based on transgenic anti-nerve growth factor antibodies. Mol Cell Neurosci 2002, 21: 15-28.
64. Houeland G, Romani A, Marchetti C, Amato G, Capsoni S, Cattaneo A, et al. Transgenic mice with chronic NGF deprivation and Alzheimer's disease-like pathology display hippocampal region-specific impairments in short- and long-term plasticities. J Neurosci 2010, 30: 13089-13094.
65. Matrone C, Di Luzio A, Meli G, D'Aguanno S, Severini C, Ciotti MT, et al. Activation of the amyloidogenic route by NGF deprivation induces apoptotic death in PC12 cells. J Alzheimers Dis 2008, 13: 81-96.
66. Matrone C, Ciotti MT, Mercanti D, Marolda R, Calissano P. NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons. Proc Natl Acad Sci U S A 2008, 105: 13139-13144.
67. Wang YJ, Wang X, Lu JJ, Li QX, Gao CY, Liu XH, et al. p75NTR regulates Abeta deposition by increasing Abeta production but inhibiting Abeta aggregation with its extracellular domain. J Neurosci 2011, 31: 2292-2304.
68. Zeng F, Lu JJ, Zhou XF, Wang YJ. Roles of p75NTR in the pathogenesis of Alzheimer's disease: a novel therapeutic target. Biochem Pharmacol 2011, 82: 1500-1509.
69. Capsoni S, Tiveron C, Vignone D, Amato G, Cattaneo A. Dissecting the involvement of tropomyosin-related kinase A and p75 neurotrophin receptor signaling in NGF deficit-induced neurodegeneration. Proc Natl Acad Sci U S A 2010, 107: 12299-12304.
70. Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010, 9: 363-372.
71. Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009, 73: 2061-2070.
72. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, et al. Long-term effects of A beta(42) immunization in Alzheimer's disease: follow-up of a randomised, placebocontrolled phase I trial. Lancet 2008, 372: 216-223.
73. Imbimbo BP, Giardina GA. Gamma-secretase inhibitors and modulators for the treatment of Alzheimer's disease: disappointments and hopes. Curr Top Med Chem 2011, 11: 1555-1570.
74. Vellas B. Tarenflurbil for Alzheimer's disease: a "shot on goal" that missed. Lancet Neurol 2010, 9: 235-237.
75. Imbimbo BP, Panza F, Frisardi V, Solfrizzi V, D'Onofrio G, Logroscino G, et al. Therapeutic intervention for Alzheimer's disease with gamma-secretase inhibitors: still a viable option? Expert Opin Investig Drugs 2011, 20: 325-341.
76. Sabbagh MN. Drug development for Alzheimer's disease: where are we now and where are we headed? Am J Geriatr Pharmacother 2009, 7: 167-185.
77. D'Alton S, George DR. Changing perspectives on Alzheimer's disease: thinking outside the amyloid box. J Alzheimers Dis 2011: Epub ahead of print.
78. Golde TE, Petrucelli L, Lewis J. Targeting Abeta and tau in Alzheimer's disease, an early interim report. Exp Neurol 2010, 223: 252-266.
79. Selkoe DJ. Resolving controversies on the path to Alzheimer's therapeutics. Nat Med 2011, 17: 1060-1065.
80. Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C. A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 2002, 3: 688-694.
81. Golde TE, Schneider LS, Koo EH. Anti-abeta therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron 2011, 69: 203-213.
82. Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 2010, 6: 108-119.
83. Berger Z, Roder H, Hanna A, Carlson A, Rangachari V, Yue M, et al. Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci 2007, 27: 3650-3662.
84. Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, et al. Defective brain microtubule assembly in Alzheimer's disease. Lancet 1986, 2: 421-426.
85. Liu R, Pei JJ, Wang XC, Zhou XW, Tian Q, Winblad B, et al. Acute anoxia induces tau dephosphorylation in rat brain slices and its possible underlying mechanisms. J Neurochem 2005, 94: 1225-1234.
86. Liu SJ, Zhang AH, Li HL, Wang Q, Deng HM, Netzer WJ, et al. Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory. J Neurochem 2003, 87: 1333-1344.
87. Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 2011, 198: 351-356.
88. Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, et al. Extended results of the Alzheimer's disease anti-inflammatory prevention trial. Alzheimers Dement 2011, 7: 402-411.
89. Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer's disease. Biochim Biophys Acta 2000, 1502: 139-144.
90. Perry G, Cash AD, Smith MA. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002, 2: 120-123.
91. Rutten BP, Steinbusch HW, Korr H, Schmitz C. Antioxidants and Alzheimer's disease: from bench to bedside (and back again). Curr Opin Clin Nutr Metab Care 2002, 5: 645-651.
92. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M. Axon regeneration requires a conserved MAP kinase pathway. Science 2009, 323: 802-806.
93. Case LC, Tessier-Lavigne M. Regeneration of the adult central nervous system. Curr Biol 2005, 15: R749-753.
94. Yuen EC, Howe CL, Li Y, Holtzman DM, Mobley WC. Nerve growth factor and the neurotrophic factor hypothesis. Brain Dev 1996, 18: 362-368.
95. Hu B, Nikolakopoulou AM, Cohen-Cory S. BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo. Development 2005, 132: 4285-4298.
96. Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, et al. Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes. J Neurosci 1996, 16: 7950-7964.
97. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, et al. Neuroprotective effects of brainderived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 2009, 15: 331-337.
98. Fjord-Larsen L, Kusk P, Emerich DF, Thanos C, Torp M, Bintz B, et al. Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer. Gene Ther 2011, 19(10): 1010-1017
99. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001, 24: 677-736.
100. Lin LF, Xue XY, Liao MJ, Xiao F, Lv RH, Luo HM. Neurotrophic effects of magnesium fructose 1, 6-diphosphate on cortical neurons. Int J Neurosci 2011, 122: 248-254.
101. Matsui N, Takahashi K, Takeichi M, Kuroshita T, Noguchi K, Yamazaki K, et al. Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice. Brain Res 2009, 1305: 108-117.
102. Alvarez XA, Cacabelos R, Sampedro C, Aleixandre M, Linares C, Granizo E, et al. Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin. Eur J Neurol 2011, 18: 59-68.
103. Muresanu DF, Rainer M, Moessler H. Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl 2002: 277-285.
104. Rossler M, Zarski R, Bohl J, Ohm TG. Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease. Acta Neuropathol 2002, 103: 363-369.
105. Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 2007, 68: 1501-1508.
106. Reiman EM, Langbaum JB, Tariot PN. Alzheimer's prevention initiative: a proposal to evaluate presymptomatic treatments as quickly as possible. Biomark Med 2010, 4: 3-14.
107. Chopra K, Misra S, Kuhad A. Current perspectives on pharmacotherapy of Alzheimer's disease. Expert Opin Pharmacother 2011, 12: 335-350.