Noradrenergic system in down syndrome and Alzheimer’s disease a target for therapy

Current Alzheimer Research

Volumn 13, Issue 1, 2016, Pages 68-83

  Phillips, Cristy ^a   Fahimi, Atoossa ^b,c   Das, Devsmita ^b,c   Mojabi, Fatemeh S ^b,c   Ponnusamy, Ravikumar ^b   Salehi, Ahmad ^b,c  

^a ARKANSAS STATE UNIVERSITY   (United States)

^b VA PALO ALTO HEALTH CARE SYSTEM   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Adrenergic system; Alzheimer s disease; Dementia; Down syndrome; Locus coeruleus; Monoaminergic systems; Adrenergic

Indexed keywords

ADRENERGIC RECEPTOR; ALDEHYDE DEHYDROGENASE; AMINE OXIDASE (FLAVIN CONTAINING); ATOMOXETINE; BRAIN DERIVED NEUROTROPHIC FACTOR; CATECHOL METHYLTRANSFERASE; DOPA DECARBOXYLASE INHIBITOR; DOPAMINE; DOPAMINE BETA MONOOXYGENASE; FORMOTEROL; LADOSTIGIL; MONOAMINE OXIDASE B INHIBITOR; NORADRENALIN; PRAZOSIN; PRODRUG; RASAGILINE; SELEGILINE; VESICULAR MONOAMINE TRANSPORTER; XAMOTEROL;

AGING; ALZHEIMER DISEASE; ANATOMICAL CONCEPTS; ARTICLE; BRAIN REGION; COGNITION; COGNITIVE DEFECT; DNA POLYMORPHISM; DOWN SYNDROME; EVIDENCE BASED PRACTICE; EXECUTIVE FUNCTION; GENETIC VARIABILITY; HUMAN; LEARNING; LOCUS CERULEUS; MEMORY; NEUROPATHOLOGY; NEUROTRANSMISSION; NONHUMAN; NORADRENERGIC SYSTEM; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN TARGETING; TRISOMY; ANIMAL; METABOLISM; PATHOLOGY;

ALZHEIMER DISEASE; ANIMALS; DOWN SYNDROME; HUMANS; LOCUS COERULEUS; NOREPINEPHRINE;

EID: 84953440014     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/1567205012666150921095924     Document Type: Article

References (206)

1. Hartley D, Blumenthal T, Carrillo M, DiPaolo G, Esralew L, Gardiner K, et al. Down syndrome and Alzheimer's disease: Common pathways, common goals. Alzheimers Dement 6: 700-9 (2015).
2. Schapiro MB, Haxby JV, Grady CL. Nature of mental retardation and dementia in Down syndrome: study with PET, CT, and neuropsychology. Neurobiol Aging 13(6): 723-34 (1992).
3. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10(2): 122-6 (1981).
4. Yates CM, Simpson J, Gordon A, Maloney AF, Allison Y, Ritchie IM, et al. Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome. Brain Res 280(1): 119-26 (1983).
5. Lanctot KL, Herrmann N, Mazzotta P, Khan LR, Ingber N. GABAergic function in Alzheimer's disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia. Can J Psychiatry 49(7): 439-53 (2004).
6. Seidl R, Cairns N, Singewald N, Kaehler ST, Lubec G. Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology. Naunyn-Schmiedeberg's Arch Pharmacol 363(2): 139-45 (2001).
7. Salehi A, Van de Nes JA, Hofman MA, Gonatas NK, Swaab DF. Early cytoskeletal changes as shown by Alz-50 are not accompanied by decreased neuronal activity. Brain Res 678(1-2): 28-39 (1995).
8. Salehi A, Gonzalez Martinez V, Swaab DF. A sex difference and no effect of ApoE type on the amount of cytoskeletal alterations in the nucleus basalis of Meynert in Alzheimer's disease. Neurobiol Aging 19(6): 505-10 (1998).
9. Aletrino MA, Vogels OJ, Van Domburg PH, Ten Donkelaar HJ. Cell loss in the nucleus raphes dorsalis in Alzheimer's disease. Neurobiol Aging 13(4): 461-8 (1992).
10. Kovacs GG, Kloppel S, Fischer I, Dorner S, Lindeck-Pozza E, Birner P, et al. Nucleus-specific alteration of raphe neurons in human neurodegenerative disorders. Neuroreport 14(1): 73-6 (2003).
11. Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Intern 45(5): 583-95 (2004).
12. Oka A, Takashima S. The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down's syndrome brains. Acta Neuropathol 97(3): 275-8 (1999).
13. Chalermpalanupap T, Kinkead B, Hu WT, Kummer MP, Hammerschmidt T, Heneka MT, et al. Targeting norepinephrine in mild cognitive impairment and Alzheimer's disease. Alzheimers Res Ther 5(2): 21 (2013).
14. Aston-Jones G, Rajkowski J, Kubiak P, Alexinsky T. Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task. J Neurosci 14(7): 4467-80 (1994).
15. Mann DM. The locus coeruleus and its possible role in ageing and degenerative disease of the human central nervous system. Mech Ageing Develop 23(1): 73-94 (1983).
16. Aston-Jones G, Ennis M, Pieribone VA, Nickell WT, Shipley MT. The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 234(4777): 734-7 (1986).
17. Arnsten AF, Goldman-Rakic PS. Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey. Brain Res 306(1-2): 9-18 (1984).
18. Loughlin SE, Foote SL, Grzanna R. Efferent projections of nucleus locus coeruleus: morphologic subpopulations have different efferent targets. Neuroscience 18(2): 307-19 (1986).
19. Jones BE, Halaris AE, McIlhany M, Moore RY. Ascending projections of the locus coeruleus in the rat. I. Axonal transport in central noradrenaline neurons. Brain Res 127(1): 1-21 (1977).
20. Moore RY, Bloom FE. Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Ann Rev Neurosci 2: 113-68 (1979).
21. Asan E. The catecholaminergic innervation of the rat amygdala. Adv Anat Embryol Cell Biol 142: 1-118 (1998).
22. Samuels ER, Szabadi E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Curr Neuropharmacol 6(3): 254-85 (2008).
23. Fornai F, di Poggio AB, Pellegrini A, Ruggieri S, Paparelli A. Noradrenaline in Parkinson's disease: from disease progression to current therapeutics. Curr Med Chem 14(22): 2330-4 (2007).
24. Fornai F, Ruffoli R, Giorgi FS, Paparelli A. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci 33(12): 2169-78 (2011).
25. Holets VR, Hokfelt T, Rokaeus A, Terenius L, Goldstein M. Locus coeruleus neurons in the rat containing neuropeptide Y, tyrosine hydroxylase or galanin and their efferent projections to the spinal cord, cerebral cortex and hypothalamus. Neuroscience 24(3): 893-906 (1988).
26. Herculano-Houzel S. The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci 3: 31 (2009).
27. Small KM, McGraw DW, Liggett SB. Pharmacology and physiology of human adrenergic receptor polymorphisms. Ann Rev Pharmacol Toxicol 43: 381-411 (2003).
28. Ordway GA, O'Donnell JM, Frazer A. Effects of clenbuterol on central beta-1 and beta-2 adrenergic receptors of the rat. J Pharmacol Exp Therap 241(1): 187-95 (1987).
29. Duman RS, Nestler EJ. Signal transduction pathways for catecholamine receptors. In: Bloom DJK, Ed. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press (1995).
30. Rababa'h A, Singh S, Suryavanshi SV, Altarabsheh SE, Deo SV, McConnell BK. Compartmentalization Role of A-Kinase Anchoring Proteins (AKAPs) in Mediating Protein Kinase A (PKA) Signaling and Cardiomyocyte Hypertrophy. Intern J Mol Sci 16(1): 218-29 (2014).
31. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79(1): 59-68 (1994).
32. Ahles A, Engelhardt S. Polymorphic variants of adrenoceptors: pharmacology, physiology, and role in disease. Pharmacol Rev 66(3): 598-637 (2014).
33. Gruart A, Benito E, Delgado-Garcia JM, Barco A. Enhanced cAMP response element-binding protein activity increases neuronal excitability, hippocampal long-term potentiation, and classical eyeblink conditioning in alert behaving mice. J Neurosci 32(48): 17431-41 (2012).
34. Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson's disease: the case for noradrenergic enhancement. Mov Disord 14: 1710-9 (2014).
35. Vijayashankar N, Brody H. A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging. J Neuropathol Exp Neurol 38(5): 490-7 (1979).
36. Fitzgerald PJ. Black bile: are elevated monoamines an etiological factor in some cases of major depression? Med Hypotheses 80(6): 823-6 (2013).
37. Ates O, Celikel FC, Taycan SE, Sezer S, Karakus N. Association between 1603C>T polymorphism of DBH gene and bipolar disorder in a Turkish population. Gene 519(2): 356-9 (2013).
38. Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol Ther 149: 150-90 (2015).
39. Garcia-Lorenzo D, Longo-Dos Santos C, Ewenczyk C, Leu-Semenescu S, Gallea C, Quattrocchi G, et al. The coeruleus/ subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson's disease. Brain 136(Pt 7): 2120-9 (2013).
40. Isaias IU, Marzegan A, Pezzoli G, Marotta G, Canesi M, Biella GE, et al. A role for locus coeruleus in Parkinson tremor. Front Hum Neurosci 5: 179 (2011).
41. Miguelez C, Aristieta A, Cenci MA, Ugedo L. The locus coeruleus is directly implicated in L-DOPA-induced dyskinesia in parkinsonian rats: an electrophysiological and behavioural study. PloS One 6(9): e24679 (2011).
42. Buchman AS, Nag S, Shulman JM, Lim AS, VanderHorst VG, Leurgans SE, et al. Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease. Mov Disord 13: 1625-31 (2012).
43. McMillan PJ, White SS, Franklin A, Greenup JL, Leverenz JB, Raskind MA, et al. Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease. Brain Res 1373: 240-52 (2011).
44. Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J Neurosci 26(2): 467-78 (2006).
45. Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60(3): 337-41 (2003).
46. Spokes EG. Neurochemical alterations in Huntington's chorea: a study of post-mortem brain tissue. Brain 103(1): 179-210 (1980).
47. Luque JM, Chan-Palay V. Alterations in tyrosine hydroxylase immunoreactive neurons of the locus ceruleus in Pick's disease. Dement Geriatr Cogn Disord 2: 291-6 (1991).
48. Thaisetthawatkul P, Boeve BF, Benarroch EE, Sandroni P, Ferman TJ, Petersen R, et al. Autonomic dysfunction in dementia with Lewy bodies. Neurology 62(10): 1804-9 (2004).
49. Akaogi Y, Asahina M, Yamanaka Y, Koyama Y, Hattori T. Sudomotor, skin vasomotor, and cardiovascular reflexes in 3 clinical forms of Lewy body disease. Neurology 73(1): 59-65 (2009).
50. Rajput A, Rajput AH. Progressive supranuclear palsy: clinical features, pathophysiology and management. Drugs Aging 18(12): 913-25 (2001).
51. Trillo L, Das D, Hsieh W, Medina B, Moghadam S, Lin B, et al. Ascending monoaminergic systems alterations in Alzheimer's disease: translating basic science into clinical care. Neurosci Biobehav Rev 37(8): 1363-79 (2013).
52. Bondareff W, Mountjoy CQ, Roth M, Rossor MN, Iversen LL, Reynolds GP, et al. Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease. Alzheimer Dis Assoc Disord 1(4): 256-62 (1987).
53. Chan-Palay V, Asan E. Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J Comp Neurol 287(3): 373-92 (1989).
54. Marcyniuk B, Mann DM, Yates PO. The topography of cell loss from locus caeruleus in Alzheimer's disease. J Neurol Sci 76(2-3): 335-45 (1986).
55. Bertrand E, Lechowicz W, Szpak GM, Dymecki J. Qualitative and quantitative analysis of locus coeruleus neurons in Parkinson's disease. Folia Neuropathol 35(2): 80-6 (1997).
56. German DC, Manaye KF, White CL, 3rd, Woodward DJ, McIntire DD, Smith WK, et al. Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32(5): 667-76 (1992).
57. Hoogendijk WJ, Pool CW, Troost D, van Zwieten E, Swaab DF. Image analyser-assisted morphometry of the locus coeruleus in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Brain 118 (Pt 1): 131-43 (1995).
58. Parvizi J, Van Hoesen GW, Damasio A. The selective vulnerability of brainstem nuclei to Alzheimer's disease. Ann Neurol 49(1): 53-66 (2001).
59. German DC, White CL, 3rd, Sparkman DR. Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21(2): 305-12 (1987).
60. Wisniewski KE, Dalton AJ, McLachlan C, Wen GY, Wisniewski HM. Alzheimer's disease in Down's syndrome: clinicopathologic studies. Neurology 35(7): 957-61 (1985).
61. Braak H, Del Tredici K. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol 121(2): 171-81 (2011).
62. Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 56(3): 331-49 (2004).
63. Hoogendijk WJ, Feenstra MG, Botterblom MH, Gilhuis J, Sommer IE, Kamphorst W, et al. Increased activity of surviving locus ceruleus neurons in Alzheimer's disease. Ann Neurol 45(1): 82-91 (1999).
64. Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM. Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging 28(3): 327-35 (2007).
65. Adolfsson R, Gottfries CG, Roos BE, Winblad B. Changes in the brain catecholamines in patients with dementia of Alzheimer type. Br J Psychiatry 135: 216-23 (1979).
66. Raskind MA, Peskind ER, Halter JB, Jimerson DC. Norepinephrine and MHPG levels in CSF and plasma in Alzheimer's disease. Arch Gen Psychiatry 41(4): 343-6 (1984).
67. Tohgi H, Ueno M, Abe T, Takahashi S, Nozaki Y. Concentrations of monoamines and their metabolites in the cerebrospinal fluid from patients with senile dementia of the Alzheimer type and vascular dementia of the Binswanger type. J Neural Transm Park Dis Dement Sect 4(1): 69-77 (1992).
68. Kopin IJ, Gordon EK, Jimerson DC, Polinsky RJ. Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol. Science 219(4580): 73-5 (1983).
69. Cross AJ, Crow TJ, Perry EK, Perry RH, Blessed G, Tomlinson BE. Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease. Br Med J 282(6258): 93-4 (1981).
70. Freedman LS, Goldstein M, Coleman M. Serum dopamine-betahydroxylase activity in Down's syndrome: a familial study. Res Comm Chem Pathol Pharmacol 8(3): 543-9 (1974).
71. Goldstein M, Freedman LS, Ebstein RP, Park DH. Studies on dopamine-beta-hydroxylase in mental disorders. J Psychiatr Res 11: 205-10 (1974).
72. Wetterberg L, Gustavson KH, Backstrom M, Ross SB, Froden O. Low dopamine-beta-hydroxylase activity in Down's syndrome. Clin Genet 3(3): 152-3 (1972).
73. Coleman M, Campbell M, Freedman LS, Roffman M, Ebstein RP, Goldstein M. Serum dopamine-beta-hydroxylase levels in Down's syndrome. Clin Genet 5(4): 312-5 (1974).
74. Gulyas B, Brockschnieder D, Nag S, Pavlova E, Kasa P, Beliczai Z, et al. The norepinephrine transporter (NET) radioligand (S, S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer's disease: a post-mortem autoradiographic study. Neurochem Intern 56(6-7): 789-98 (2010).
75. Tejani-Butt SM, Yang J, Zaffar H. Norepinephrine transporter sites are decreased in the locus coeruleus in Alzheimer's disease. Brain Res 631(1): 147-50 (1993).
76. Yates CM, Ritchie IM, Simpson J, Maloney AF, Gordon A. Noradrenaline in Alzheimer-type dementia and Down syndrome. Lancet 2(8236): 39-40 (1981).
77. Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M. Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue. J Neurol Neurosur Psychiatry 50(6): 775-8 (1987).
78. Risser D, Lubec G, Cairns N, Herrera-Marschitz M. Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. Life Sci 60(15): 1231-7 (1997).
79. Reynolds GP, Godridge H. Alzheimer-like brain monoamine deficits in adults with Down's syndrome. Lancet 2(8468): 1368-9 (1985).
80. Kay AD, Schapiro MB, Riker AK, Haxby JV, Rapoport SI, Cutler NR. Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down's syndrome. Ann Neurol 21(4): 408-11 (1987).
81. Schapiro MB, Kay AD, May C, Ryker AK, Haxby JV, Kaufman S, et al. Cerebrospinal fluid monoamines in Down's syndrome adults at different ages. J Ment Defic Res 31 (Pt 3): 259-69 (1987).
82. Dekker AD, Coppus AM, Vermeiren Y, Aerts T, van Duijn CM, Kremer BP, et al. Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with Down syndrome. J Alzheimer's Dis 43(3): 871-91 (2015).
83. Combarros O, Warden DR, Hammond N, Cortina-Borja M, Belbin O, Lehmann MG, et al. The dopamine beta-hydroxylase-1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project. BMC Med Genet 11: 162 (2010).
84. Martinez MF, Martin XE, Alcelay LG, Flores JC, Valiente JM, Juanbeltz BI, et al. The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers. BMC Neurosci 10: 125 (2009).
85. Lanni C, Garbin G, Lisa A, Biundo F, Ranzenigo A, Sinforiani E, et al. Influence of COMT Val158Met polymorphism on Alzheimer's disease and mild cognitive impairment in Italian patients. J Alzheimers Dis 32(4): 919-26 (2012).
86. Yu JT, Tan L, Ou JR, Zhu JX, Liu K, Song JH, et al. Polymorphisms at the beta2-adrenergic receptor gene influence Alzheimer's disease susceptibility. Brain Res 1210: 216-22 (2008).
87. Koutroumani M, Daniilidou M, Giannakouros T, Proitsi P, Liapi D, Germanou A, et al. The deletion variant of alpha2b-adrenergic receptor is associated with decreased risk in Alzheimer's disease and mild cognitive impairment. J Neurol Sci 328(1-2): 19-23 (2013).
88. Kirstein SL, Insel PA. Autonomic nervous system pharmacogenomics: a progress report. Pharmacol Rev 56(1): 31-52(2004).
89. Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, et al. A quantitative-trait analysis of human plasmadopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Human Genet 68(2): 515-22 (2001).
90. Weinshilboum RM, Axelrod J. Reduced plasma dopamine-betahydroxylase activity in familial dysautonomia. New Eng J Med 285(17): 938-42 (1971).
91. Lieberman AN, Freedman LS, Goldstein M. Serum dopamine-betahydroxylase activity in patients with Huntington's chorea and Parkinson's disease. Lancet 1(7742): 153-4 (1972).
92. Fujita K, Ito T, Maruta K, Teradaira R, Beppu H, Nakagami Y, et al. Serum dopamine-beta-hydroxylase in schizophrenic patients. J Neurochem 30(6): 1569-72 (1978).
93. Perry EK, Tomlinson BE, Blessed G, Perry RH, Cross AJ, Crow TJ. Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease. J Neurol Sci 51(2): 279-87 (1981).
94. Mustapic M, Presecki P, Pivac N, Mimica N, Hof PR, Simic G, et al. Genotype-independent decrease in plasma dopamine beta hydroxylase activity in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 44: 94-9 (2013).
95. Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, et al. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci USA 95(17): 9991-6 (1998).
96. Lachman HM, Morrow B, Shprintzen R, Veit S, Parsia SS, Faedda G, et al. Association of codon 108/158 catechol-Omethyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet 67(5): 468-72 (1996).
97. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, et al. Kinetics of human soluble and membrane-bound catechol Omethyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34(13): 4202-10 (1995).
98. Blasi G, Mattay VS, Bertolino A, Elvevag B, Callicott JH, Das S, et al. Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci 25(20): 5038-45 (2005).
99. de Frias CM, Annerbrink K, Westberg L, Eriksson E, Adolfsson R, Nilsson LG. Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults. J Cogn Neurosci 17(7): 1018-25 (2005).
100. Harris SE, Wright AF, Hayward C, Starr JM, Whalley LJ, Deary IJ. The functional COMT polymorphism, Val 158 Met, is associated with logical memory and the personality trait intellect/imagination in a cohort of healthy 79 year olds. Neurosci Lett 385(1): 1-6 (2005).
101. Wang PN, Liu HC, Liu TY, Chu A, Hong CJ, Lin KN, et al. Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease. Dement Geriatr Cogn Disord 19(2-3): 120-5 (2005).
102. Lee YH, Song GG. COMT Val158Met and PPARgamma Pro12Ala polymorphisms and susceptibility to Alzheimer's disease: a metaanalysis. Neurol Sci 35(5): 643-51 (2014).
103. Hesse C, Eisenach JH. Genetic variation in the β(2)-adrenergic receptor: impact on intermediate cardiovascular phenotypes. Curr Pharmacogenom Person Med 6(3): 160-70 (2008).
104. Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, et al. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol 63(5): 686-92 (2006).
105. Dishy V, Sofowora GG, Xie HG, Kim RB, Byrne DW, Stein CM, et al. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. New Eng J Med 345(14): 1030-5 (2001).
106. Small KM, Brown KM, Forbes SL, Liggett SB. Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization. J Biol Chem 276(7): 4917-22 (2001).
107. Knusel B, Beck KD, Winslow JW, Rosenthal A, Burton LE, Widmer HR, et al. Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci 12(11): 4391-402 (1992).
108. Friedman WJ, Ibanez CF, Hallbook F, Persson H, Cain LD, Dreyfus CF, et al. Differential actions of neurotrophins in the locus coeruleus and basal forebrain. Exp Neurol 119(1): 72-8 (1993).
109. Korte M, Kang H, Bonhoeffer T, Schuman E. A role for BDNF in the late-phase of hippocampal long-term potentiation. Neuropharmacol 37(4-5): 553-9 (1998).
110. Witte AV, Kurten J, Jansen S, Schirmacher A, Brand E, Sommer J, et al. Interaction of BDNF and COMT polymorphisms on pairedassociative stimulation-induced cortical plasticity. J Neurosci 32(13): 4553-61 (2012).
111. Sanchez MM, Das D, Taylor JL, Noda A, Yesavage JA, Salehi A. BDNF polymorphism predicts the rate of decline in skilled task performance and hippocampal volume in healthy individuals. Trans Psychiatry 1: e51 (2011).
112. Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, et al. NGF is essential for hippocampal plasticity and learning. J Neurosci 29(35): 10883-9 (2009).
113. Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol 57(4): 451-84 (1999).
114. Lin Y, Cheng S, Xie Z, Zhang D. Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis. PloS One 9(4): e94961 (2014).
115. Dogliotti G, Galliera E, Licastro F, Corsi MM. Age-related changes in plasma levels of BDNF in Down syndrome patients. Immunity Ageing: I & A. 7: 2 (2010).
116. Holm PC, Rodriguez FJ, Kresse A, Canals JM, Silos-Santiago I, Arenas E. Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons. Development 130(15): 3535-45 (2003).
117. Hunter CL, Bachman D, Granholm AC. Minocycline prevents cholinergic loss in a mouse model of Down's syndrome. Ann Neurol 56(5): 675-88 (2004).
118. Hunter CL, Bimonte HA, Granholm AC. Behavioral comparison of 4 and 6 month-old Ts65Dn mice: age-related impairments in working and reference memory. Behav Brain Res 138(2): 121-31 (2003).
119. Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, et al. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51(1): 29-42 (2006).
120. Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, et al. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci USA 98(18): 10439-44 (2001).
121. Holtzman DM, Li Y, Chen K, Gage FH, Epstein CJ, Mobley WC. Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration. Neurology 43(12): 2668-73 (1993).
122. Granholm AC, Sanders LA, Crnic LS. Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome. Exp Neurol 2000; 161(2): 647-63 (2000).
123. Dierssen M, Vallina IF, Baamonde C, Garcia-Calatayud S, Lumbreras MA, Florez J. Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Brain Res 749(2): 238-44 (1997).
124. Demas GE, Nelson RJ, Krueger BK, Yarowsky PJ. Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res 82(1): 85-92 (1996).
125. Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, et al. Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. Sci Trans Med 1(7): 7ra17 (2009).
126. Salehi A, Kleshevnikov A, Mobley WC. Cholinergic neurodegenration in Alzheimer's disease: basis for nerve growth factor therapy. In: Cueollo AC, Ed. Pharmacological Mechanisms in Alzheimer's Therapies, USA: Springer (2007).
127. Liu ME, Hong CJ, Liou YJ, Tsai YL, Hsieh CH, Tsai SJ. Association study of a functional catechol-O-methyltransferase polymorphism and executive function in elderly males without dementia. Neurosci Lett 436(2): 193-5 (2008).
128. German DC, Nelson O, Liang F, Liang CL, Games D. The PDAPP mouse model of Alzheimer's disease: locus coeruleus neuronal shrinkage. J Compar Neurol 492(4): 469-76 (2005).
129. O'Neil JN, Mouton PR, Tizabi Y, Ottinger MA, Lei DL, Ingram DK, et al. Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice. J Chen Neuroanot 34(3-4): 102-7 (2007).
130. Liu L, Luo S, Zeng L, Wang W, Yuan L, Jian X. Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer's disease. Neural Regen Res 8(24): 2249-55 (2013).
131. Pugh PL, Richardson JC, Bate ST, Upton N, Sunter D. Noncognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease. Behav Brain Res 178(1): 18-28 (2007).
132. Kalinin S, Polak PE, Lin SX, Sakharkar AJ, Pandey SC, Feinstein DL. The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease. Neurobiol Aging 33(8): 1651-63 (2012).
133. Dang V, Medina B, Das D, Moghadam S, Martin KJ, Lin B, et al. Formoterol, a long-acting beta2 adrenergic agonist, improves cog nitive function and promotes dendritic complexity in a mouse model of Down syndrome. Biol Psychiatry 75(3): 179-88 (2014).
134. Belichenko PV, Kleschevnikov AM, Salehi A, Epstein CJ, Mobley WC. Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. Cochrane Database Syst Rev 504(4): 329-45 (2007).
135. Lockrow JP, Fortress AM, Granholm AC. Age-related neurodegeneration and memory loss in Down syndrome. Curr Gerontol Geriatr Res 2012: 463909 (2012).
136. Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157(1): 277-86 (2000).
137. Poon WW, Blurton-Jones M, Tu CH, Feinberg LM, Chabrier MA, Harris JW, et al. beta-Amyloid impairs axonal BDNF retrograde trafficking. Neurobiol Aging 32(5): 821-33 (2011).
138. Liu X, Ye K, Weinshenker D. Norepinephrine Protects against Amyloid-beta Toxicity via TrkB. J Alzheimer's Dis 44(1): 251-60 (2015).
139. Ressler KJ, Nemeroff CB. Role of norepinephrine in the pathophysiology of neuropsychiatric disorders. CNS Spectr 6(8): 663-6, 70 (2001).
140. Kalaria RN, Andorn AC. Adrenergic receptors in aging and Alzheimer's disease: decreased alpha 2-receptors demonstrated by [3H]p-aminoclonidine binding in prefrontal cortex. Neurobiol Aging 12(2): 131-6 (1991).
141. Khakpour-Taleghani B, Lashgari R, Motamedi F, Naghdi N. Effect of reversible inactivation of locus ceruleus on spatial reference and working memory. Neuroscience 158(4): 1284-91 (2009).
142. van Stegeren AH. The role of the noradrenergic system in emotional memory. Acta Psychol 127(3): 532-41 (2008).
143. Rodrigues SM, LeDoux JE, Sapolsky RM. The influence of stress hormones on fear circuitry. Ann Rev Neurosci 32: 289-313 (2009).
144. Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10(3): 211-23 (2009).
145. Sterpenich V, D'Argembeau A, Desseilles M, Balteau E, Albouy G, Vandewalle G, et al. The locus ceruleus is involved in the successful retrieval of emotional memories in humans. J Neurosci 26(28): 7416-23 (2006).
146. Galvez R, Mesches MH, McGaugh JL. Norepinephrine release in the amygdala in response to footshock stimulation. Neurobiol Learn Mem 66(3): 253-7 (1996).
147. McIntyre CK, Hatfield T, McGaugh JL. Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats. Eur J Neurosci 16(7): 1223-6 (2002).
148. Tanaka T, Yokoo H, Mizoguchi K, Yoshida M, Tsuda A, Tanaka M. Noradrenaline release in the rat amygdala is increased by stress: studies with intracerebral microdialysis. Brain Res 544(1): 174-6 (1991).
149. Gallagher M, Kapp BS, Musty RE, Driscoll PA. Memory formation: evidence for a specific neurochemical system in the amygdala. Science 198(4315): 423-5 (1977).
150. Ikegaya Y, Nakanishi K, Saito H, Abe K. Amygdala betanoradrenergic influence on hippocampal long-term potentiation in vivo. Neuroreport 8(14): 3143-6 (1997).
151. Tully K, Bolshakov VY. Emotional enhancement of memory: how norepinephrine enables synaptic plasticity. Mol Brain 3: 15 (2010).
152. Crowe SF, Shaw S. Salbutamol overcomes the effect of the noradrenergic neurotoxin DSP-4 on memory function in the dayold chick. Behav Pharmacol 8(2-3): 216-22 (1997).
153. Cahill L, McGaugh JL. A novel demonstration of enhanced memory associated with emotional arousal. Conscios Cogn 4(4): 410-21 (1995).
154. Cahill L, Prins B, Weber M, McGaugh JL. Beta-adrenergic activation and memory for emotional events. Nature 371(6499): 702-4 (1994).
155. van Stegeren AH, Everaerd W, Cahill L, McGaugh JL, Gooren LJ. Memory for emotional events: differential effects of centrally versus peripherally acting beta-blocking agents. Psychopharmacology 138(3-4): 305-10 (1998).
156. Kaufmann H, Saadia D, Voustianiouk A, Goldstein DS, Holmes C, Yahr MD, et al. Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation 108(6): 724-8 (2003).
157. Mathias CJ. L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res 18(1): 25-9 (2008).
158. Kaufmann H. L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res 18(1): 19-24 (2008).
159. Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology 83(4): 328-35 (2014).
160. Fortress AM, Hamlett ED, Vazey EM, Aston-Jones G, Cass WA, Boger HA, et al. Designer receptors enhance memory in a mouse model of Down syndrome. J Neurosci 35(4): 1343-53 (2015).
161. Kummer MP, Hammerschmidt T, Martinez A, Terwel D, Eichele G, Witten A, et al. Ear2 deletion causes early memory and learning deficits in APP/PS1 mice. J Neurosci 34(26): 8845-54 (2014).
162. Jardanhazi-Kurutz D, Kummer MP, Terwel D, Vogel K, Thiele A, Heneka MT. Distinct adrenergic system changes and neuroinflammation in response to induced locus ceruleus degeneration in APP/PS1 transgenic mice. Neuroscience 176: 396-407 (2011).
163. Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7(4): 295-309(2006).
164. Sparks DL, Woeltz VM, Markesbery WR. Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease. Arch Neurol 48(7): 718-21 (1991).
165. Saura J, Luque JM, Cesura AM, Da Prada M, Chan-Palay V, Huber G, et al. Increased monoamine oxidase B activity in plaqueassociated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography. Neuroscience 62(1): 15-30 (1994).
166. Sano M, Ernesto C, Klauber MR, Schafer K, Woodbury P, Thomas R, et al. Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 10(3): 132-40 (1996).
167. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. New Engl J Med 336(17): 1216-22 (1997).
168. Wilcock GK, Birks J, Whitehead A, Evans SJ. The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. Intern J Geriatr Psychiatry 17(2): 175-83 (2002).
169. Birks J, Flicker L. Selegiline for Alzheimer's disease. Cochrane Database Syst Rev CD000442 (2003).
170. Gallagher DA, Schrag A. Impact of newer pharmacological treatments on quality of life in patients with Parkinson's disease. CNS Drugs 22(7): 563-86 (2008).
171. Weinreb O, Amit T, Bar-Am O, Youdim MB. Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurol 92(3): 330-44 (2010).
172. Maruyama W, Nitta A, Shamoto-Nagai M, Hirata Y, Akao Y, Yodim M, et al. N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor. Neurochem Intern 44(6): 393-400 (2004).
173. Maruyama W, Youdim MB, Naoi M. Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022. Ann NY Acad Sci 39: 320-9 (2001).
174. Akao Y, Maruyama W, Shimizu S, Yi H, Nakagawa Y, Shamoto-Nagai M, et al. Mitochondrial permeability transition mediates apoptosis induced by N-methyl(R)salsolinol, an endogenous neurotoxin, and is inhibited by Bcl-2 and rasagiline, N-propargyl-1(R)-aminoindan. J Neurochem 82(4): 913-23 (2002).
175. Youdim MB, Weinstock M. Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(Npropargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol 21(6): 555-73 (2001).
176. Weinreb O, Bar-Am O, Prosolovich K, Amit T, Youdim MB. Does 1-(R)-aminoindan possess neuroprotective properties against experimental Parkinson's disease? Antioxid Redox Signal 14(5): 767-75 (2011).
177. Huang W, Chen Y, Shohami E, Weinstock M. Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse. Eur J Pharmacol 366(2-3): 127-35 (1999).
178. Sagi Y, Mandel S, Amit T, Youdim MB. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 25(1): 35-44 (2007).
179. Clinicaltrials.gov.
180. Weinreb O, Amit T, Bar-Am O, Youdim MB. A novel anti-Alzheimer's disease drug, ladostigil neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor. Int Rev Neurobiol 100: 191-215 (2011).
181. Sagi Y, Drigues N, Youdim MB. The neurochemical and behavioral effects of the novel cholinesterase-monoamine oxidase inhibitor, ladostigil, in response to L-dopa and L-tryptophan, in rats. Br J Pharmacol 146(4): 553-60 (2005).
182. Yogev-Falach M, Bar-Am O, Amit T, Weinreb O, Youdim MB. A multifunctional, neuroprotective drug, ladostigil (TV3326), regulates holo-APP translation and processing. FASEB J 20(12): 2177-9 (2006).
183. www.ClinicalTrials.gov NCT01354691
184. Hammerness P, McCarthy K, Mancuso E, Gendron C, Geller D. Atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a review. Neuropsychiatr Dis Treat 2009; 5: 215-26.
185. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/ hyperactivity disorder. Neuropsychopharmacology 27(5): 699-711 (2002).
186. Wong DT, Threlkeld PG, Best KL, Bymaster FP. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther 222(1): 61-5 (1982).
187. Heil SH, Holmes HW, Bickel WK, Higgins ST, Badger GJ, Laws HF, et al. Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users. Drug Alcohol Depend 67(2): 149-56 (2002).
188. Dang V, Martin K, Moghadam S, Medina B, Lin B, Patel D, Salehi A, Eds. Improving noradrenergic signaling in the treatment of cognitive dysfunction in the Ts65Dn mouse model of Down syndrome. New Orleans: Society for Neuroscience (2012).
189. Tzavara ET, Bymaster FP, Overshiner CD, Davis RJ, Perry KW, Wolff M, et al. Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine. Mol Psychiatry 11(2): 187-95 (2006).
190. Davis JA, Gould TJ. Atomoxetine reverses nicotine withdrawalassociated deficits in contextual fear conditioning. Neuropsychopharmacology 32(9): 2011-9 (2007).
191. Mohs RC, Shiovitz TM, Tariot PN, Porsteinsson AP, Baker KD, Feldman PD. Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-month, randomized, double-blind, placebo-controlled, parallel-trial study. Am J Geriatr Psychiatry (9): 752-9 (2009).
192. de Jong CG, Van De Voorde S, Roeyers H, Raymaekers R, Allen AJ, Knijff S, et al. Differential effects of atomoxetine on executive functioning and lexical decision in attention-deficit/hyperactivity disorder and reading disorder. J Child Adoles Psychopharmacol 19(6): 699-707 (2009).
193. Gau SS, Shang CY. Improvement of executive functions in boys with attention deficit hyperactivity disorder: an open-label followup study with once-daily atomoxetine. Int J Neuropsychopharmacol 13(2): 243-56 (2010).
194. Brown TE, Holdnack J, Saylor K, Adler L, Spencer T, Williams DW, et al. Effect of atomoxetine on executive function impairments in adults with ADHD. J Attention Disord 15(2): 130-8 (2011).
195. Katsouri L, Vizcaychipi MP, McArthur S, Harrison I, Suarez-Calvet M, Lleo A, et al. Prazosin, an alpha(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiol Aging 34(4): 1105-15 (2013).
196. Wang LY, Shofer JB, Rohde K, Hart KL, Hoff DJ, McFall YH, et al. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry 17(9): 744-51 (2009).
197. Marlow HF. The efficacy of xamoterol in heart failure of ischemic origin. J Cardiovacol Pharmacol 14(5): S69-72.
198. Schutsky K, Ouyang M, Thomas SA. Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled beta2-adrenergic signaling. Learn Mem 18(9): 598-604 (2011).
199. Faizi M, Bader PL, Tun C, Encarnacion A, Kleschevnikov A, Belichenko P, et al. Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiol J 43(2): 397-413 (2011).
200. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. New Engl J 337(20): 1405-11 (1997).
201. Das D, Phillips C, Hsieh W, Sumanth K, Dang V, Salehi A. Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome. Prog Neuro-psychopharmacol Biol Psychiatry 54: 140-8 (2014).
202. Phillips C, Baktir MA, Srivatsan M, Salehi A. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci 170: (2014).
203. Phillips C, Baktir, M.A., Das, D., Linn, B., Salehi A. The Link Between Physical Activity and Alzheimer's Disease. Phy Ther J (2015).
204. Aston-Jones G, Gold JI. How we say no: norepinephrine, inferior frontal gyrus, and response inhibition. Biol Psychiatry 65(7): 548-9 (2009).
205. Das D, Phillips, C., Lin B., Mojabi, F., Hsieh, W., Dang, V., Salehi, A. Assessment of dendritic arborization in the dentate gyrus of the hippocampal region in mice. J Vis Exp 97: (2015).
206. Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, et al. Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and Down syndrome. Neurobiol Aging 25(10): 1263-72 (2004).