Dementia in Down's syndrome

The Lancet Neurology

Volumn 15, Issue 6, 2016, Pages 622-636

  Ballard, Clive ^a   Mobley, William ^b   Hardy, John ^c   Williams, Gareth ^a   Corbett, Anne ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; AMYLOID ANTIBODY; ANTIOXIDANT; NEUROTRANSMITTER; NOOTROPIC AGENT; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; CEREBROSPINAL FLUID; CHROMOSOME 21; DEMENTIA; DIAGNOSTIC PROCEDURE; DOWN SYNDROME; EARLY DIAGNOSIS; GENETIC RISK; HUMAN; NERVOUS SYSTEM DEVELOPMENT; NEUROIMAGING; NEUROPATHOLOGY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; TRISOMY; COMORBIDITY; GENETICS; METABOLISM;

COMORBIDITY; DEMENTIA; DOWN SYNDROME; HUMANS;

EID: 84962862398     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(16)00063-6     Document Type: Review

References (152)

1. Hanney M, Prasher V, Williams N, et al. Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial. Lancet 2012, 379:528-536.
2. Stancliffe RJ LK, Larson SA, Engler J, Taub S, Fortune J, Bershadsky J Demographic characteristics, health conditions, and residential service use in adults with Down syndrome in 25 U.S. states. Intellect Dev Disabil 2012, 50:92-108.
3. Margallo-Lana ML, Moore PB, Kay DW, et al. Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology. J Intellect Disabil Res 2007, 51:463-477.
4. Coppus A, Evenhuis H, Verberne GJ, et al. Dementia and mortality in persons with Down's syndrome. J Intellect Disabil Res 2006, 50:768-777.
5. Tyrrell J, Cosgrave M, McCarron M, et al. Dementia in people with Down's syndrome. Int J Geriatr Psychiatry 2001, 16:1168-1174.
6. Holland AJ, Hon J, Huppert FA, Stevens F Incidence and course of dementia in people with Down's syndrome: findings from a population-based study. J Intellect Disabil Res 2000, 44:138-146.
7. Holland AJ, Hon J, Huppert FA, Stevens F, Watson P Population-based study of the prevalence and presentation of dementia in adults with Down's syndrome. Br J Psychiatry 1998, 172:493-498.
8. Oliver C, Crayton L, Holland A, Hall S, Bradbury J A four year prospective study of age-related cognitive change in adults with Down's syndrome. Psychol Med 1998, 28:1365-1377.
9. Sekijima Y, Ikeda S, Tokuda T, et al. Prevalence of dementia of Alzheimer type and apolipoprotein E phenotypes in aged patients with Down's syndrome. Eur Neurol 1998, 39:234-237.
10. Visser FE, Aldenkamp AP, van Huffelen AC, Kuilman M, Overweg J, van Wijk J Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome. Am J Ment Retard 1997, 101:400-412.
11. Devenny DA, Silverman WP, Hill AL, Jenkins E, Sersen EA, Wisniewski KE Normal ageing in adults with Down's syndrome: a longitudinal study. J Intellect Disabil Res 1996, 40:208-221.
12. Zigman WB, Schupf N, Sersen E, Silverman W Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard 1996, 100:403-412.
13. Prasher VP Age-specific prevalence, thyroid dysfunction and depressive symptomatology in adults with Down syndrome and dementia. Int J Geriatr Psychiatry 1995, 10:25-31.
14. Brugge KL, Nichols SL, Salmon DP, et al. Cognitive impairment in adults with Down's syndrome: similarities to early cognitive changes in Alzheimer's disease. Neurology 1994, 44:232-238.
15. Franceschi M, Comola M, Piattoni F, Gualandri W, Canal N Prevalence of dementia in adult patients with trisomy 21. Am J Med Genet Suppl 1990, 7:306-308.
16. Evenhuis HM The natural history of dementia in Down's syndrome. Arch Neurol 1990, 47:263-267.
17. Lai F, Williams RS A prospective study of Alzheimer disease in Down syndrome. Arch Neurol 1989, 46:849-853.
18. Zigman WB Atypical aging in Down syndrome. Dev Disabil Res Rev 2013, 18:51-67.
19. Margallo-Lana ML, Ballard C, Morris C, Kay D, Tyrer S, Moore B Cognitive decline in Down syndrome. Arch Neurol 2003, 60:1024.
20. Jones EL, Aarsland D, Londos E, Ballard C A pilot study examining associations between DYRK1A and alpha-synuclein dementias. Neurodegener Dis 2012, 10:229-231.
21. Oliver C, Holland T, Hall S, Crayton L Effects of increasing task load on memory impairment in adults with Down syndrome. Am J Ment Retard 2005, 110:339-345.
22. Collacott RA, Cooper S-A A five-year follow up study of adaptive behaviour in adults with Down syndrome. J Int Dev Dis 1997, 22:187-197.
23. Menendez M Down syndrome, Alzheimer's disease and seizures. Brain Dev 2005, 27:246-252.
24. Ekstein S, Glick B, Weill M, Kay B, Berger I Down syndrome and attention-deficit/hyperactivity disorder (ADHD). J Child Neurol 2011, 26:1290-1295.
25. Ball SL, Holland AJ, Huppert FA, Treppner P, Watson P, Hon J The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome. J Intellect Disabil Res 2004, 48:611-620.
26. Sahakian BJ, Morris RG, Evenden JL, et al. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain 1988, 111:695-718.
27. Nelson LD, Scheibel KE, Ringman JM, Sayre JW An experimental approach to detecting dementia in Down syndrome: a paradigm for Alzheimer's disease. Brain Cogn 2007, 64:92-103.
28. Mann DM, Royston MC, Ravindra CR Some morphometric observations on the brains of patients with Down's syndrome: their relationship to age and dementia. J Neurol Sci 1990, 99:153-164.
29. Haier RJ, Head K, Head E, Lott IT Neuroimaging of individuals with Down's syndrome at-risk for dementia: evidence for possible compensatory events. NeuroImage 2008, 39:1324-1332.
30. Sabbagh MN, Chen K, Rogers J, et al. Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia. Alzheimers Dement 2015, 11:994-1004.
31. Teipel SJ, Alexander GE, Schapiro MB, Moller HJ, Rapoport SI, Hampel H Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain 2004, 127:811-824.
32. Haier RJ, Alkire MT, White NS, et al. Temporal cortex hypermetabolism in Down syndrome prior to the onset of dementia. Neurology 2003, 61:1673-1679.
33. Jennings D, Seibyl J, Sabbagh M, et al. Age dependence of brain beta-amyloid deposition in Down syndrome: an [18F]florbetaben PET study. Neurology 2015, 84:500-507.
34. Hof PR, Bouras C, Perl DP, Sparks DL, Mehta N, Morrison JH Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Quantitative regional analysis and comparison with Alzheimer's disease. Arch Neurol 1995, 52:379-391.
35. Handen BL, Cohen AD, Channamalappa U, et al. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B. Alzheimers Dement 2012, 8:496-501.
36. Nelson LD, Siddarth P, Kepe V, et al. Positron emission tomography of brain beta-amyloid and tau levels in adults with Down syndrome. Arch Neurol 2011, 68:768-774.
37. Mann DM, Esiri MM The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome. J Neurol Sci 1989, 89:169-179.
38. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 2001, 357:169-175. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).
39. Jack CR, Holtzman DM Biomarker modeling of Alzheimer's disease. Neuron 2013, 80:1347-1358.
40. Head E, Lott IT, Hof PR, et al. Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome. J Neuropathol Exp Neurol 2003, 62:917-926.
41. Bertrand D, Koffas D Cas d'idiotie mongolienne adulte avec nombrueses plaues seniles et concretions calcarires pallidales. Revista de Neurologia 1946, 78:338-343.
42. Struwe F Histopathology untersuchungen uber entstenhung und wesen der senile plaques. Z Ges Neurol Psychiatr 1929, 122:291-307.
43. Portelius E, Holtta M, Soininen H, et al. Altered cerebrospinal fluid levels of amyloid beta and amyloid precursor-like protein 1 peptides in Down's syndrome. Neuromolecular Med 2014, 16:510-516.
44. Cosentino SA, Stern Y, Sokolov E, et al. Plasma β-amyloid and cognitive decline. Arch Neurol 2010, 67:1485-1490.
45. Coppus AM, Schuur M, Vergeer J, et al. Plasma beta amyloid and the risk of Alzheimer's disease in Down syndrome. Neurobiol Aging 2012, 33:1988-1994.
46. Schupf N, Patel B, Pang D, et al. Elevated plasma beta-amyloid peptide Aβ(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol 2007, 64:1007-1013.
47. Matsuoka Y, Andrews HF, Becker AG, et al. The relationship of plasma Abeta levels to dementia in aging individuals with Down syndrome. Alzheimer Dis Assoc Disord 2009, 23:315-318.
48. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis 1996, 3:16-32.
49. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E Alzheimer's disease. Lancet 2011, 377:1019-1031.
50. Hirayama A, Horikoshi Y, Maeda M, Ito M, Takashima S Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome. Brain Dev 2003, 25:180-185.
51. 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 2000, 157:277-286.
52. Jiang Y, Mullaney KA, Peterhoff CM, et al. Alzheimer's-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition. Proc Natl Acad Sci USA 2010, 107:1630-1635.
53. Shinohara M, Sato N, Kurinami H, et al. Reduction of brain beta-amyloid (Abeta) by fluvastatin, a hydroxymethylglutaryl-CoA reductase inhibitor, through increase in degradation of amyloid precursor protein C-terminal fragments (APP-CTFs) and Abeta clearance. J Biol Chem 2010, 285:22091-22102.
54. Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue. J Neurol Neurosurg Psychiatry 1987, 50:775-778.
55. Hijazi M, Fillat C, Medina JM, Velasco A Overexpression of DYRK1A inhibits choline acetyltransferase induction by oleic acid in cellular models of Down syndrome. Exp Neurol 2013, 239:229-234.
56. Ross MH, Galaburda AM, Kemper TL Down's syndrome: is there a decreased population of neurons?. Neurology 1984, 34:909-916.
57. Bhattacharyya A, McMillan E, Chen SI, Wallace K, Svendsen CN A critical period in cortical interneuron neurogenesis in down syndrome revealed by human neural progenitor cells. Dev Neurosci 2009, 31:497-510.
58. 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 Schmiedebergs Arch Pharmacol 2001, 363:139-145.
59. Best TK, Cramer NP, Chakrabarti L, Haydar TF, Galdzicki Z Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome. Exp Neurol 2012, 233:749-757.
60. Kleschevnikov AM, Belichenko PV, Villar AJ, Epstein CJ, Malenka RC, Mobley WC Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J Neurosci 2004, 24:8153-8160.
61. Belichenko PV, Kleschevnikov AM, Salehi A, Epstein CJ, Mobley WC Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. J Comp Neurol 2007, 504:329-345.
62. 1H MRS). J Neurodev Disord 2014, 6:42.
63. McCarron MO, Nicoll JA, Graham DI A quartet of Down's syndrome, Alzheimer's disease, cerebral amyloid angiopathy, and cerebral haemorrhage: interacting genetic risk factors. J Neurol Neurosurg Psychiatry 1998, 65:405-406.
64. Lippa CF, Schmidt ML, Lee VM, Trojanowski JQ Antibodies to alpha-synuclein detect Lewy bodies in many Down's syndrome brains with Alzheimer's disease. Ann Neurol 1999, 45:353-357.
65. Lippa CF, Rosso AL, Stutzbach LD, Neumann M, Lee VM, Trojanowski JQ Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome. Arch Neurol 2009, 66:1483-1488.
66. Gardiner K, Davisson M The sequence of human chromosome 21 and implications for research into Down syndrome. Genome Biol 2000, 1. REVIEWS0002.
67. Wiseman FK, Al-Janabi T, Hardy J, et al. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci 2015, 16:564-574.
68. Sleegers K, Brouwers N, Gijselinck I, et al. APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain 2006, 129:2977-2983.
69. Cabrejo L, Guyant-Marechal L, Laquerriere A, et al. Phenotype associated with APP duplication in five families. Brain 2006, 129:2966-2976.
70. Kasuga K, Shimohata T, Nishimura A, et al. Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease. J Neurol Neurosurg Psychiatry 2009, 80:1050-1052.
71. Korbel JO, Tirosh-Wagner T, Urban AE, et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci USA 2009, 106:12031-12036.
72. Seregaza Z, Roubertoux PL, Jamon M, Soumireu-Mourat B Mouse models of cognitive disorders in trisomy 21: a review. Behav Genet 2006, 36:387-404.
73. Matsui T, Ingelsson M, Fukumoto H, et al. Expression of APP pathway mRNAs and proteins in Alzheimer's disease. Brain Res 2007, 1161:116-123.
74. Johnson SA, McNeill T, Cordell B, Finch CE Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer's disease. Science 1990, 248:854-857.
75. Higgins LS, Catalano R, Quon D, Cordell B Transgenic mice expressing human beta-APP751, but not mice expressing beta-APP695, display early Alzheimer's disease-like histopathology. Ann N Y Acad Sci 1993, 695:224-227.
76. Li L, Perry R, Wu J, et al. Polymorphic tetranucleotide repeat site within intron 7 of the beta-amyloid precursor protein gene and its lack of association with Alzheimer's disease. Hum Genet 1998, 103:86-89.
77. Margallo-Lana M, Morris CM, Gibson AM, et al. Influence of the amyloid precursor protein locus on dementia in Down syndrome. Neurology 2004, 62:1996-1998.
78. Jones EL, Ballard CG, Prasher VP, et al. An intron 7 polymorphism in APP affects the age of onset of dementia in Down syndrome. Int J Alzheimers Dis 2010, 2011:929102.
79. Beyreuther K, Pollwein P, Multhaup G, et al. Regulation and expression of the Alzheimer's beta/A4 amyloid protein precursor in health, disease, and Down's syndrome. Ann N Y Acad Sci 1993, 695:91-102.
80. Li Y, Wang H, Wang S, Quon D, Liu YW, Cordell B Positive and negative regulation of APP amyloidogenesis by sumoylation. Proc Natl Acad Sci USA 2003, 100:259-264.
81. Wang X, Huang T, Zhao Y, et al. Sorting nexin 27 regulates Abeta production through modulating gamma-secretase activity. Cell Rep 2014, 9:1023-1033.
82. Mok KY, Jones EL, Hanney M, et al. Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome. Neurobiol Aging 2014, 35:1513.e1-1513.e5.
83. Yu Y, Jia J Lack of association between the polymorphisms of beta-site APP-cleaving enzyme 2 (BACE2) 5'-flanking region and sporadic Alzheimer's disease. Brain Res 2009, 1257:10-15.
84. Sun X, He G, Song W BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J 2006, 20:1369-1376.
85. Azkona G, Amador-Arjona A, Obradors-Tarrago C, et al. Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2. Genes Brain Behav 2010, 9:160-172.
86. Arron JR, Winslow MM, Polleri A, et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 2006, 441:595-600.
87. Yang EJ, Ahn YS, Chung KC Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells. J Biol Chem 2001, 276:39819-39824.
88. Wegiel J, Gong CX, Hwang YW The role of DYRK1A in neurodegenerative diseases. FEBS J 2011, 278:236-245.
89. Guedj F, Sebrie C, Rivals I, et al. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS One 2009, 4:e4606.
90. Ahn KJ, Jeong HK, Choi HS, et al. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 2006, 22:463-472.
91. Rotilio G, Aquilano K, Ciriolo MR Interplay of Cu, Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes. IUBMB Life 2003, 55:629-634.
92. Phillips AC, Sleigh A, McAllister CJ, et al. Defective mitochondrial function in vivo in skeletal muscle in adults with Down's syndrome: a 31P-MRS study. PLoS One 2013, 8:e84031.
93. Gatt AP, Jones EL, Francis PT, Ballard C, Bateman JM Association of a polymorphism in mitochondrial transcription factor A (TFAM) with Parkinson's disease dementia but not dementia with Lewy bodies. Neurosci Lett 2013, 557(pt B):177-180.
94. Coskun PE, Wyrembak J, Derbereva O, et al. Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and Down syndrome dementia. J Alzheimers Dis 2010, 20(suppl 2):S293-S310.
95. Cagin U, Duncan OF, Gatt AP, Dionne MS, Sweeney ST, Bateman JM Mitochondrial retrograde signaling regulates neuronal function. Proc Natl Acad Sci USA 2015, 112:E6000-E6009.
96. Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate. J Biol Chem 2002, 277:17597-17604.
97. Wilcock DM, Griffin WS Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J Neuroinflammation 2013, 10:84.
98. Phillips MC Molecular mechanisms of cellular cholesterol efflux. J Biol Chem 2014, 289:24020-24029.
99. Kim WS, Rahmanto AS, Kamili A, et al. Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-beta peptide generation. J Biol Chem 2007, 282:2851-2861.
100. Lujan R, Marron Fernandez de Velasco E, Aguado C, Wickman K New insights into the therapeutic potential of Girk channels. Trends Neurosci 2014, 37:20-29.
101. Williams G A searchable cross-platform gene expression database reveals connections between drug treatments and disease. BMC Genomics 2012, 13:12.
102. Liang WS, Dunckley T, Beach TG, et al. Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set. Physiol Genomics 2008, 33:240-256.
103. Hodges A, Strand AD, Aragaki AK, et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 2006, 15:965-977.
104. Moran LB, Duke DC, Deprez M, Dexter DT, Pearce RK, Graeber MB Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease. Neurogenetics 2006, 7:1-11.
105. Roses AD, Saunders AM, Corder EH, et al. Influence of the susceptibility genes apolipoprotein E-epsilon 4 and apolipoprotein E-epsilon 2 on the rate of disease expressivity of late-onset Alzheimer's disease. Arzneimittelforschung 1995, 45:413-417.
106. Cedazo-Minguez A Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities. J Cell Mol Med 2007, 11:1227-1238.
107. Deb S, Braganza J, Norton N, et al. APOE epsilon 4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome. Br J Psychiatry 2000, 176:468-472.
108. Prasher VP, Sajith SG, Rees SD, et al. Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down syndrome. Int J Geriatr Psychiatry 2008, 23:1134-1140.
109. Hyman BT, West HL, Rebeck GW, et al. Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proc Natl Acad Sci USA 1995, 92:3586-3590.
110. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 1988, 85:4051-4055.
111. Russ C, Powell JF, Zhao J, et al. The microtubule associated protein tau gene and Alzheimer's disease-an association study and meta-analysis. Neurosci Lett 2001, 314:92-96.
112. Jones EL, Margallo-Lana M, Prasher VP, Ballard CG The extended tau haplotype and the age of onset of dementia in Down syndrome. Dement Geriatr Cogn Disord 2008, 26:199-202.
113. Jones EL, Mok K, Hanney M, et al. Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome. Neurobiol Aging 2013, 34:2441.e1-2441.e5.
114. Alzforum AlzGene-funnel plot for polymorphism RS8106922, (accessed July 2, 2015). http://www.alzgene.org/funnel.asp?geneID=463&polyID=2211.
115. Xu W, Tan L, Yu JT The role of PICALM in Alzheimer's disease. Mol Neurobiol 2015, 52:399-413.
116. Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007, 39:168-177.
117. Lee JH, Chulikavit M, Pang D, Zigman WB, Silverman W, Schupf N Association between genetic variants in sortilin-related receptor 1 (SORL1) and Alzheimer's disease in adults with Down syndrome. Neurosci Lett 2007, 425:105-109.
118. Patel A, Rees SD, Kelly MA, et al. Association of variants within APOE, SORL1, RUNX1, BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome. Neurosci Lett 2011, 487:144-148.
119. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease 2011, National Institute for Clinical Excellence, London, (accessed March 11, 2013). http://www.nice.org.uk/guidance/ta217.
120. Qaseem A, Snow V, Cross JT, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2008, 148:370-378.
121. Mohan M, Carpenter PK, Bennett C Donepezil for dementia in people with Down syndrome. Cochrane Database Syst Rev 2009, 1. CD007178.
122. Prasher VP, Fung N, Adams C Rivastigmine in the treatment of dementia in Alzheimer's disease in adults with Down syndrome. Int J Geriatr Psychiatry 2005, 20:496-497.
123. Prasher VP, Sachdeva N, Adams C, Haque MS Rivastigmine transdermal patches in the treatment of dementia in Alzheimer's disease in adults with Down syndrome-pilot study. Int J Geriatr Psychiatry 2013, 28:219-220.
124. de Souza FM, Busquet N, Blatner M, Maclean KN, Restrepo D Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome. Sci Rep 2011, 1:137.
125. Press release: world's first clinical trial for anti-Abeta vaccine targeting Alzheimer's disease-like characteristics in people with Down syndrome. AC Immune Jan 7, 2016, (accessed March 11, 2016). http://acimmune.com/content/news2/acimmune_downsyndrome_20160107.pdf.
126. Netzer WJ, Powell C, Nong Y, et al. Lowering beta-amyloid levels rescues learning and memory in a Down syndrome mouse model. PLoS One 2010, 5:e10943.
127. Liu CC, Kanekiyo T, Xu H, Bu G Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013, 9:106-118.
128. Smith JC, Nielson KA, Woodard JL, et al. Interactive effects of physical activity and APOE-epsilon4 on BOLD semantic memory activation in healthy elders. Neuroimage 2011, 54:635-644.
129. Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 2014, 311:33-44.
130. Lockrow J, Prakasam A, Huang P, Bimonte-Nelson H, Sambamurti K, Granholm AC Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model. Exp Neurol 2009, 216:278-289.
131. Shichiri M, Yoshida Y, Ishida N, et al. Alpha-tocopherol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome. Free Radic Biol Med 2011, 50:1801-1811.
132. Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A 2011, 155A:1939-1948.
133. Kriz J, Nguyen MD, Julien JP Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2002, 10:268-278.
134. Hunter CL, Bachman D, Granholm AC Minocycline prevents cholinergic loss in a mouse model of Down's syndrome. Ann Neurol 2004, 56:675-688.
135. Costa AC, Scott-McKean JJ Prospects for improving brain function in individuals with Down syndrome. CNS Drugs 2013, 27:679-702.
136. Catuara-Solarz S, Espinosa-Carrasco J, Erb I, et al. Principal component analysis of the effects of environmental enrichment and (-)-epigallocatechin-3-gallate on age-associated learning deficits in a mouse model of Down syndrome. Front Behav Neurosci 2005, 9:330.
137. De la Torre R, De Sola S, Pons M, et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res 2014, 58:278-288.
138. Abbassi R, Johns TG, Kassiou M, Munoz L DYRK1A in neurodegeneration and cancer: molecular basis and clinical implications. Pharmacol Ther 2015, 151:87-98.
139. Kobayashi T, Washiyama K, Ikeda K Inhibition of G protein-activated inwardly rectifying K+ channels by fluoxetine (Prozac). Br J Pharmacol 2003, 138:1119-1128.
140. Prasher VP Seizures associated with fluoxetine therapy. Seizure 1993, 2:315-317.
141. Guilloux JP, Mendez-David I, Pehrson A, et al. Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice. Neuropharmacology 2013, 73:147-159.
142. Blurton-Jones M, Kitazawa M, Martinez-Coria H, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 2009, 106:13594-13599.
143. Hassani Z, O'Reilly J, Pearse Y, et al. Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke. PLoS One 2012, 7:e50444.
144. Fernandez F, Morishita W, Zuniga E, et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci 2007, 10:411-413.
145. Braudeau J, Delatour B, Duchon A, et al. Specific targeting of the GABA-A receptor alpha5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice. J Psychopharmacol 2011, 25:1030-1042.
146. Faizi M, Bader PL, Tun C, 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 Dis 2011, 43:397-413.
147. Das I, Reeves RH The use of mouse models to understand and improve cognitive deficits in Down syndrome. Dis Model Mech 2011, 4:596-606.
148. Iulita MF, Do Carmo S, Ower AK, et al. Nerve growth factor metabolic dysfunction in Down's syndrome brains. Brain 2014, 137:860-872.
149. Lamb J, Crawford ED, Peck D, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 2006, 313:1929-1935.
150. Liu X, Ye K, Weinshenker D Norepinephrine protects against amyloid-beta toxicity via TrkB. J Alzheimers Dis 2015, 44:251-260.
151. Williams G Searchable platform-independent expression database (accessed March 11, 2016). http://www.spied.org.uk/cgi-bin/SPIED_DS_CMAP_RESULTS.cgi?GSE5390_CMAP_RESULTS.html.
152. Ferreira N, Owen A, Mohan A, Corbett A, Ballard C Association between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline. Int J Geriatr Psychiatry 2014, 30:422-430.