Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease

Neurobiology of Disease

Volumn 71, Issue , 2014, Pages 110-130

  Kazim, Syed Faraz ^a,b,c   Blanchard, Julie ^a   Dai, Chun Ling ^a   Tung, Yunn Chyn ^a   LaFerla, Frank M ^d   Iqbal, Inge Grundke ^a   Iqbal, Khalid ^a  

^a NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

^b SUNY DOWNSTATE MEDICAL CENTER   (United States)

^c SUNY IBR Center for Developmental Neuroscience (CDN)   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; Amyloid beta; Brain derived neurotrophic factor (BDNF); Ciliary neurotrophic factor (CNTF) derived peptide; Cognition; Dendritic and synaptic plasticity; Glycogen synthase kinase 3 beta (GSK3 ); Neurogenesis; Tau hyperphosphorylation

Indexed keywords

AMYLOID BETA PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; CILIARY NEUROTROPHIC FACTOR; GLYCOGEN SYNTHASE KINASE 3BETA; PEPTIDE 021; PHOSPHATIDYLINOSITOL 3 KINASE; TAU PROTEIN; UNCLASSIFIED DRUG; AMYLOID PRECURSOR PROTEIN; ENZYME INHIBITOR; NEUROLEPTIC AGENT; PRESENILIN 1; NEUROTROPHIC FACTOR;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY; ARTICLE; BIOACCUMULATION; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DENTATE GYRUS; DRUG MECHANISM; DRUG STRUCTURE; FEMALE; HIPPOCAMPAL CA1 REGION; LONG TERM CARE; MENTAL TASK; MOUSE; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RECOGNITION; REFERENCE MEMORY; SPATIAL MEMORY; WILD TYPE; ANIMAL; BLOOD; BLOOD TESTIS BARRIER; BRAIN; C57BL MOUSE; CELL CULTURE; CHEMISTRY; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; MALE; NERVE CELL; ORAL DRUG ADMINISTRATION; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TIME; TRANSGENIC MOUSE; ADULT; BRAIN LEVEL; BRAIN TISSUE; COGNITIVE DEFECT; DIET SUPPLEMENTATION; DISEASE SEVERITY; DRUG EFFICACY; DRUG PENETRATION; ELEVATED PLUS MAZE TEST; MORRIS WATER MAZE TEST; NEUROPATHOLOGY; OPEN FIELD TEST; PATTERN RECOGNITION; PROTEIN AGGREGATION; PROTEIN ANALYSIS; TREATMENT DURATION;

ADMINISTRATION, ORAL; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ANTIPSYCHOTIC AGENTS; BLOOD-TESTIS BARRIER; BRAIN; CELLS, CULTURED; CILIARY NEUROTROPHIC FACTOR; DISEASE MODELS, ANIMAL; ENZYME INHIBITORS; FEMALE; GENE EXPRESSION REGULATION; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEURONS; PRESENILIN-1; SIGNAL TRANSDUCTION; TAU PROTEINS; TIME FACTORS;

EID: 84906561770     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.07.001     Document Type: Article

References (114)

1. ACTSG A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 1996, 46:1244-1249.
2. Akarsu E.S., Bishai I., Coceani F. Effect of ciliary neurotrophic factor on body temperature and cerebrospinal fluid prostanoids in the cat. Brain Res. Bull. 1998, 45:9-14.
3. Anggono V., Huganir R.L. Regulation of AMPA receptor trafficking and synaptic plasticity. Curr. Opin. Neurobiol. 2012, 22:461-469.
4. Arendt T. Synaptic degeneration in Alzheimer's disease. Acta Neuropathol. 2009, 118:167-179.
5. Artero S., Tierney M.C., Touchon J., Ritchie K. Prediction of transition from cognitive impairment to senile dementia: a prospective, longitudinal study. Acta Psychiatr. Scand. 2003, 107:390-393.
6. Bath K.G., Akins M.R., Lee F.S. BDNF control of adult SVZ neurogenesis. Dev. Psychobiol. 2012, 54:578-589.
7. Bensadoun A., Weinstein D. Assay of proteins in the presence of interfering materials. Anal. Biochem. 1976, 70:241-250.
8. Billings L.M., Oddo S., Green K.N., McGaugh J.L., LaFerla F.M. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 2005, 45:675-688.
9. Blanchard J., Chohan M.O., Li B., Liu F., Iqbal K., Grundke-Iqbal I. Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice. J. Alzheimers Dis. 2010, 21:1185-1195.
10. Blanchard J., Wanka L., Tung Y.C., Cardenas-Aguayo Mdel C., LaFerla F.M., Iqbal K., Grundke-Iqbal I. Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Abeta and tau pathologies in 3xTg-AD mice. Acta Neuropathol. 2010, 120:605-621.
11. Blanchard J., Bolognin S., Chohan M.O., Rabe A., Iqbal K., Grundke-Iqbal I. Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome. J. Neuropathol. Exp. Neurol. 2011, 70:1070-1079.
12. Blurton-Jones M., Kitazawa M., Martinez-Coria H., Castello N.A., Muller F.J., Loring J.F., Yamasaki T.R., Poon W.W., Green K.N., LaFerla F.M. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:13594-13599.
13. Bolognin S., Blanchard J., Wang X., Basurto-Islas G., Tung Y.C., Kohlbrenner E., Grundke-Iqbal I., Iqbal K. An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol. 2012, 123:133-151.
14. Bolognin S., Buffelli M., Puoliväli J., Iqbal K. Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiol. Aging 2014, 35(9):2134-2146.
15. Cardenas-Aguayo Mdel C., Santa-Olalla J., Baizabal J.M., Salgado L.M., Covarrubias L. Growth factor deprivation induces an alternative non-apoptotic death mechanism that is inhibited by Bcl2 in cells derived from neural precursor cells. J. Hematother. Stem Cell Res. 2003, 12:735-748.
16. Cardenas-Aguayo Mdel C., Kazim S.F., Grundke-Iqbal I., Iqbal K. Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures. PLoS One 2013, 8:e53596.
17. Carroll J.C., Rosario E.R., Kreimer S., Villamagna A., Gentzschein E., Stanczyk F.Z., Pike C.J. Sex differences in β-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure. Brain Res. 2010, 1366:233-245.
18. Chen Z.Y., Cao L., Wang L.M., Guo C., Ye J.L., Chai Y.F., Yan Z.Y. Development of neurotrophic molecules for treatment of neurodegeneration. Curr. Protein Pept. Sci. 2001, 2(3):261-276.
19. Chen H., Tung Y.C., Li B., Iqbal K., Grundke-Iqbal I. Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis. Neurobiol. Aging 2007, 28(8):1148-1162.
20. Chen Y., Liang Z., Blanchard J., Dai C.L., Sun S., Lee M.H., Grundke-Iqbal I., Iqbal K., Liu F., Gong C.X. A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse). Mol. Neurobiol. 2013, 47:711-725.
21. Chohan M.O., Li B., Blanchard J., Tung Y.C., Heaney A.T., Rabe A., Iqbal K., Grundke-Iqbal I. Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol. Aging 2011, 32:1420-1434.
22. Clinton L.K., Billings L.M., Green K.N., Caccamo A., Ngo J., Oddo S., McGaugh J.L., LaFerla F.M. Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol. Dis. 2007, 28:76-82.
23. Collingridge G.L., Volianskis A., Bannister N., France G., Hanna L., Mercier M., Tidball P., Fang G., Irvine M.W., Costa B.M., Monaghan D.T., Bortolotto Z.A., Molnar E., Lodge D., Jane D.E. The NMDA receptor as a target for cognitive enhancement. Neuropharmacology 2013, 64:13-26.
24. Connor B., Young D., Yan Q., Faull R.L., Synek B., Dragunow M. Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Brain research. Mol. Brain Res. 1997, 49:71-81.
25. Corona C., Masciopinto F., Silvestri E., Viscovo A.D., Lattanzio R., Sorda R.L., Ciavardelli D., Goglia F., Piantelli M., Canzoniero L.M., Sensi S.L. Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction. Cell Death Dis. 2010, 1:e91.
26. Couillard-Despres S., Winner B., Schaubeck S., Aigner R., Vroemen M., Weidner N., Bogdahn U., Winkler J., Kuhn H.G., Aigner L. Doublecortin expression levels in adult brain reflect neurogenesis. Eur. J. Neurosci. 2005, 21:1-14.
27. Cross D.A., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995, 378:785-789.
28. Cuadrado-Tejedor M., Hervias I., Ricobaraza A., Puerta E., Perez-Roldan J.M., Garcia-Barroso C., Franco R., Aguirre N., Garcia-Osta A. Sildenafil restores cognitive function without affecting beta-amyloid burden in a mouse model of Alzheimer's disease. Br. J. Pharmacol. 2011, 164:2029-2041.
29. DaRocha-Souto B., Coma M., Perez-Nievas B.G., Scotton T.C., Siao M., Sanchez-Ferrer P., Hashimoto T., Fan Z., Hudry E., Barroeta I., Sereno L., Rodriguez M., Sanchez M.B., Hyman B.T., Gomez-Isla T. Activation of glycogen synthase kinase-3 beta mediates beta-amyloid induced neuritic damage in Alzheimer's disease. Neurobiol. Dis. 2012, 45:425-437.
30. Davies C.A., Mann D.M., Sumpter P.Q., Yates P.O. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J. Neurol. Sci. 1987, 78:151-164.
31. Davis K.E., Eacott M.J., Easton A., Gigg J. Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice. Behav. Brain Res. 2013, 254:73-82.
32. Dawbarn D., Allen S.J. Neurotrophins and neurodegeneration. Neuropathol. Appl. Neurobiol. 2003, 29:211-230.
33. Demars M., Hu Y.S., Gadadhar A., Lazarov O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J. Neurosci. Res. 2010, 88:2103-2117.
34. Dobarro M., Orejana L., Aguirre N., Ramirez M.J. Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model. Neuropharmacology 2013, 64:137-144.
35. Donovan M.H., Yazdani U., Norris R.D., Games D., German D.C., Eisch A.J. Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. J. Comp. Neurol. 2006, 495:70-83.
36. Egeland M., Zhang X., Millan M.J., Mocaer E., Svenningsson P. Pharmacological or genetic blockade of the dopamine D3 receptor increases cell proliferation in the hippocampus of adult mice. J. Neurochem. 2012, 123:811-823.
37. Elliott E., Atlas R., Lange A., Ginzburg I. Brain-derived neurotrophic factor induces a rapid dephosphorylation of tau protein through a PI-3 Kinase signalling mechanism. Eur. J. Neurosci. 2005, 22:1081-1089.
38. Ennaceur A. One-trial objects recognition in rats and mice: methodological and theoritical issues. Behav. Brain Res. 2010, 215:244-254.
39. Frisardi V., Solfrizzi V., Imbimbo P.B., Capurso C., D'Introno A., Colacicco A.M., Vendemiale G., Seripa D., Pilotto A., Capurso A., Panza F. Towards disease-modifying treatment of Alzheimer's disease: drugs targeting beta-amyloid. Curr. Alzheimer Res. 2010, 7:40-55.
40. Fuster-Matanzo A., Llorens-Martín M., Hernández F., Avila J. Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediat. Inflamm. 2013, 2013:260925.
41. Garcia P., Youssef I., Utvik J.K., Florent-Bechard S., Barthelemy V., Malaplate-Armand C., Kriem B., Stenger C., Koziel V., Olivier J.L., Escanye M.C., Hanse M., Allouche A., Desbene C., Yen F.T., Bjerkvig R., Oster T., Niclou S.P., Pillot T. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease. J. Neurosci. 2010, 30:7516-7527.
42. Glenner G.G., Wong C.W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984, 120:885-890.
43. Granger A.J., Shi Y., Lu W., Cerpas M., Nicoll R.A. LTP requires a reserve pool of glutamate receptors independent of subunit type. Nature 2013, 493:495-500.
44. Grundke-Iqbal I., Iqbal K., Tung Y.C., Quinlan M., Wisniewski H.M., Binder L.I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. U. S. A. 1986, 83:4913-4917.
45. Grundke-Iqbal I., Vorbrodt A.W., Iqbal K., Tung Y.C., Wang G.P., Wisniewski H.M. Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments. Brain Res. 1988, 464:43-52.
46. Hebert L.E., Weuve J., Scherr P.A., Evans D.A. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology 2013, 80:1778-1783.
47. Heldt S.A., Stanek L., Chhatwal J.P., Ressler K.J. Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol. Psychiatry 2007, 12:656-670.
48. Hernandez F., Borrell J., Guaza C., Avila J., Lucas J.J. Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J. Neurochem. 2002, 83:1529-1533.
49. Hirata-Fukae C., Li H.F., Hoe H.S., Gray A.J., Minami S.S., Hamada K., Niikura T., Hua F., Tsukagoshi-Nagai H., Horikoshi-Sakuraba Y., Mughal M., Rebeck G.W., LaFerla F.M., Mattson M.P., Iwata N., Saido T.C., Klein W.L., Duff K.E., Aisen P.S., Matsuoka Y. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 2008, 1216:92-103.
50. Hu S., Begum A.N., Jones M.R., Oh M.S., Beech W.K., Beech B.H., Yang F., Chen P., Ubeda O.J., Kim P.C., Davies P., Ma Q., Cole G.M., Frautschy S.A. GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol. Dis. 2009, 33:193-206.
51. Hunter J.M., Bowers W.J., Maarouf C.L., Mastrangelo M.A., Daugs I.D., Kokjohn T.A., Kalback W.M., Luehrs D.C., Valla J., Beach T.G., Roher A.E. Biochemical and morphological characterization of the AbetaPP/PS/tau triple transgenic mouse model and its relevance to sporadic Alzheimer's disease. J. Alzheimers Dis. 2011, 27:361-376.
52. Iqbal K., Grundke-Iqbal I. Alzheimer's disease, a multifactorial disorder seeking multitherapies. Alzheimers Dement. 2010, 6:420-424.
53. Iqbal K., Grundke-Iqbal I. Opportunities and challenges in developing Alzheimer disease therapeutics. Acta Neuropathol. 2011, 122:543-549.
54. Iqbal K., Flory M., Khatoon S., Soininen H., Pirttila T., Lehtovirta M., Alafuzoff I., Blennow K., Andreasen N., Vanmechelen E., Grundke-Iqbal I. Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers. Ann. Neurol. 2005, 58:748-757.
55. Jacob A.C., Zmuda J.M., Cauley J.A., Metter E.J., Hurley B.F., Ferrell R.E., Roth S.M. Ciliary neurotrophic factor (CNTF) genotype and body composition. European journal of human genetics. Eur. J. Hum. Genet. 2004, 12:372-376.
56. Janz R., Sudhof T.C., Hammer R.E., Unni V., Siegelbaum S.A., Bolshakov V.Y. Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 1999, 24:687-700.
57. Jin K., Xie L., Childs J., Sun Y., Mao X.O., Logvinova A., Greenberg D.A. Cerebral neurogenesis is induced by intranasal administration of growth factors. Ann. Neurol. 2003, 53:405-409.
58. Kee N., Sivalingam S., Boonstra R., Wojtowicz J.M. The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J. Neurosci. Methods 2002, 115:97-105.
59. Kern D.S., Maclean K.N., Jiang H., Synder E.Y., Sladek J.R., Bjugstad K.B. Neural stem cells reduce hippocampal tau and reelin accumulation in aged Ts65Dn Down syndrome mice. Cell Transplant. 2010, 20:371-379.
60. Kessels H.W., Malinow R. Synaptic AMPA receptor plasticity and behavior. Neuron 2009, 61:340-350.
61. King M.K., Pardo M., Cheng Y., Downey K., Jope R.S., Beurel E. Glycogen synthase kinase-3 inhibitors: Rescuers of cognitive impairments. Pharmacol. Ther. 2014, 141(1):1-12.
62. Kitazawa M., Oddo S., Yamasaki T.R., Green K.N., LaFerla F.M. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J. Neurosci. 2005, 25:8843-8853.
63. Kiyota T., Ingraham K.L., Jacobsen M.T., Xiong H., Ikezu T. FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:E1339-E1348.
64. Koizumi S., Contreras M.L., Matsuda Y., Hama T., Lazarovici P., Guroff G. K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells. J. Neurosci. 1988, 8:715-721.
65. Kokoeva M.V., Yin H., Flier J.S. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 2005, 310:679-683.
66. Lahiani-Cohen I., Lourbopoulos A., Haber E., Rozenstein-Tsalkovich L., Abramsky O., Grigoriadis N., Rosenmann H. Moderate environmental enrichment mitigates tauopathy in a neurofibrillary tangle mouse model. J. Neuropathol. Exp. Neurol. 2011, 70:610-621.
67. Li B., Yamamori H., Tatebayashi Y., Shafit-Zagardo B., Tanimukai H., Chen S., Iqbal K., Grundke-Iqbal I. Failure of neuronal maturation in Alzheimer disease dentate gyrus. J. Neuropathol. Exp. Neurol. 2008, 67:78-84.
68. Li B., Wanka L., Blanchard J., Liu F., Chohan M.O., Iqbal K., Grundke-Iqbal I. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett. 2010, 584:3359-3365.
69. Lichtenwalner R.J., Forbes M.E., Bennett S.A., Lynch C.D., Sonntag W.E., Riddle D.R. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 2001, 107:603-613.
70. Longo F.M., Yang T., Knowles J.K., Xie Y., Moore L.A., et al. Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms. Curr Alzheimer Res 2007, 4:503-506.
71. Lu B., Nagappan G., Guan X., Nathan P.J., Wren P. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat. Rev. Neurosci. 2013, 14(6):401-416.
72. Ma M., Ma Y., Yi X., Guo R., Zhu W., Fan X., Xu G., Frey W.H., Liu X. Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone. BMC Neurosci. 2008, 9:117.
73. Malberg J.E., Eisch A.J., Nestler E.J., Duman R.S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 2000, 20:9104-9110.
74. Malenka R.C., Bear M.F. LTP and LTD: an embarrassment of riches. Neuron 2004, 44:5-21.
75. Martino G., Pluchino S. The therapeutic potential of neural stem cells. Nat. Rev. Neurosci. 2006, 7:395-406.
76. McGeer E.G., McGeer P.L. Inflammatory processes in Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2003, 27:741-749.
77. Meng Y., Zhang Y., Jia Z. Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3. Neuron 2003, 39:163-176.
78. Morris R.G., Garrud P., Rawlins J.N., O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 1982, 297:681-683.
79. Nagahara A.H., Merrill D.A., Coppola G., Tsukada S., Schroeder B.E., Shaked G.M., Wang L., Blesch A., Kim A., Conner J.M., Rockenstein E., Chao M.V., Koo E.H., Geschwind D., Masliah E., Chiba A.A., Tuszynski M.H. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat. Med. 2009, 15:331-337.
80. Nagahara A.H., Mateling M., Kovacs I., Wang L., Eggert S., Rockenstein E., Koo E.H., Masliah E., Tuszynski M.H. Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice. J. Neurosci. 2013, 33(39):15596-15602.
81. Neves G., Cooke S.F., Bliss T.V. Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat. Rev. Neurosci. 2008, 9:65-75.
82. Oddo S., Caccamo A., Shepherd J.D., Murphy M.P., Golde T.E., Kayed R., Metherate R., Mattson M.P., Akbari Y., LaFerla F.M. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003, 39:409-421.
83. Panza F., Solfrizzi V., Frisardi V., Capurso C., D'Introno A., Colacicco A.M., Vendemiale G., Capurso A., Imbimbo B.P. Disease-modifying approach to the treatment of Alzheimer's disease: from alpha-secretase activators to gamma-secretase inhibitors and modulators. Drugs Aging 2009, 26:537-555.
84. Panza F., Solfrizzi V., Frisardi V., Imbimbo B.P., Capurso C., D'Introno A., Colacicco A.M., Seripa D., Vendemiale G., Capurso A., Pilotto A. Beyond the neurotransmitter-focused approach in treating Alzheimer's disease: drugs targeting beta-amyloid and tau protein. Aging Clin. Exp. Res. 2009, 21:386-406.
85. Panza F., Frisardi V., Solfrizzi V., Imbimbo B.P., Logroscino G., Santamato A., Greco A., Seripa D., Pilotto A. Immunotherapy for Alzheimer's disease: from anti-beta-amyloid to tau-based immunization strategies. Immunotherapy 2012, 4:213-238.
86. Pei J.J., Gong C.X., Iqbal K., Grundke-Iqbal I., Wu Q.L., Winblad B., Cowburn R.F. Subcellular distribution of protein phosphatases and abnormally phosphorylated tau in the temporal cortex from Alzheimer's disease and control brains. J. Neural Transm. 1998, 105:69-83.
87. Phiel C.J., Wilson C.A., Lee V.M., Klein P.S. GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 2003, 423:435-439.
88. Rachubinski A.L., Maclean K.N., Evans J.R., Bjugstad K.B. Modulating cognitive deficits and tau accumulation in a mouse model of aging Down syndrome through neonatal implantation of neural progenitor cells. Exp. Gerontol. 2012, 47:723-733.
89. Redmond D.E., Bjugstad K.B., Teng Y.D., Ourednik V., Ourednik J., Wakeman D.R., Parsons X.H., Gonzalez R., Blanchard B.C., Kim S.U., Gu Z., Lipton S.A., Markakis E.A., Roth R.H., Elsworth J.D., Sladek J.R., Sidman R.L., Snyder E.Y. Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:12175-12180.
90. Rohe M., Synowitz M., Glass R., Paul S.M., Nykjaer A., Willnow T.E. Brain-derived neurotrophic factor reduces amyloidogenic processing through control of SORLA gene expression. J. Neurosci. 2009, 29:15472-15478.
91. Rosario E.R., Carroll J.C., Oddo S., LaFerla F.M., Pike C.J. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J. Neurosci. 2006, 26:13384-13389.
92. Sairanen M., Lucas G., Ernfors P., Castren M., Castren E. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J. Neurosci. 2005, 25:1089-1094.
93. Sanderson D.J., Good M.A., Seeburg P.H., Sprengel R., Rawlins J.N., Bannerman D.M. The role of the GluR-A (GluR1) AMPA receptor subunit in learning and memory. Prog. Brain Res. 2008, 169:159-178.
94. Sargolini F., Roullet P., Oliverio A., Mele A. Effects of intra-accumbens focal administrations of glutamate antagonists on object recognition memory in mice. Behav. Brain Res. 2003, 138:153-163.
95. Scheff S.W., Price D.A., Schmitt F.A., Mufson E.J. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol. Aging 2006, 27:1372-1384.
96. Scheff S.W., Price D.A., Schmitt F.A., DeKosky S.T., Mufson E.J. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 2007, 68:1501-1508.
97. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science 2002, 298:789-791.
98. Sereno L., Coma M., Rodriguez M., Sanchez-Ferrer P., Sanchez M.B., Gich I., Agullo J.M., Perez M., Avila J., Guardia-Laguarta C., Clarimon J., Lleo A., Gomez-Isla T. A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol. Dis. 2009, 35:359-367.
99. Shafit-Zagardo B., Kalcheva N. Making sense of the multiple MAP-2 transcripts and their role in the neuron. Mol. Neurobiol. 1998, 16:149-162.
100. Shao C.Y., Mirra S.S., Sait H.B., Sacktor T.C., Sigurdsson E.M. Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease. Acta Neuropathol. 2011, 122:285-292.
101. Shruster A., Melamed E., Offen D. Neurogenesis in the aged and neurodegenerative brain. Apoptosis 2010, 15:1415-1421.
102. Simpson J.E., Ince P.G., Lace G., Forster G., Shaw P.J., Matthews F., Savva G., Brayne C., Wharton SB MRC Cognitive Function and Ageing Neuropathology Study Group. Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol. Aging 2010, 31(4):578-590.
103. Spillantini M.G., Iovino M., Vuono R. Release of growth factors by neuronal precursor cells as a treatment for diseases with tau pathology. Arch. Ital. Biol. 2011, 149:215-223.
104. Sze C.I., Troncoso J.C., Kawas C., Mouton P., Price D.L., Martin L.J. Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J. Neuropathol. Exp. Neurol. 1997, 56:933-944.
105. Tapley P., Lamballe F., Barbacid M. K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors. Oncogene 1992, 7:371-381.
106. Tatebayashi Y., Iqbal K., Grundke-Iqbal I. Dynamic regulation of expression and phosphorylation of tau by fibroblast growth factor-2 in neural progenitor cells from adult rat hippocampus. J. Neurosci. 1999, 19:5245-5254.
107. Terry R.D., Masliah E., Salmon D.P., Butters N., DeTeresa R., Hill R., Hansen L.A., Katzman R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 1991, 30:572-580.
108. Vallet P.G., Guntern R., Hof P.R., Golaz J., Delacourte A., Robakis N.K., Bouras C. A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease. Acta Neuropathol. 1992, 83:170-178.
109. Wang J.Z., Wu Q., Smith A., Grundke-Iqbal I., Iqbal K. Tau is phosphorylated by GSK-3 at several sites found in Alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by A-kinase. FEBS Lett. 1998, 436:28-34.
110. Wang J.Z., Grundke-Iqbal I., Iqbal K. Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur. J. Neurosci. 2007, 25(1):59-68.
111. Welsh K.A., Butters N., Hughes J.P., Mohs R.C., Heyman A. Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease. Arch. Neurol. 1992, 49:448-452.
112. Wyss-Coray T., Rogers J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med. 2012, 2:a006346.
113. Xiong H., Futamura T., Jourdi H., Zhou H., Takei N., Diverse-Pierluissi M., Plevy S., Nawa H. Neurotrophins induce BDNF expression through the glutamate receptor pathway in neocortical neurons. Neuropharmacology 2002, 42:903-912.
114. Zamanillo D., Sprengel R., Hvalby O., Jensen V., Burnashev N., Rozov A., Kaiser K.M., Koster H.J., Borchardt T., Worley P., Lubke J., Frotscher M., Kelly P.H., Sommer B., Andersen P., Seeburg P.H., Sakmann B. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 1999, 284:1805-1811.