Insights from mouse models to understand neurodegeneration in down syndrome

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 4, 2010, Pages 429-438

  Fillat, Cristina ^a   Dierssen, Mara ^a   de Lagrán, María Martínez ^a   Altafaj, Xavier ^a  

^a CENTRE FOR GENOMIC REGULATION CRG   (Spain)

Author keywords

Alzheimer's disease; Down syndrome; Hsa21 genes; Mouse models; Neurodegeneration

Indexed keywords

AMYLOID PRECURSOR PROTEIN; COPPER ZINC SUPEROXIDE DISMUTASE;

ALZHEIMER DISEASE; APP GENE; ARTICLE; BACE2 GENE; DOWN SYNDROME; DYRK1A GENE; GENE; GENE OVEREXPRESSION; HSA21 GENE; HUMAN; INCIDENCE; MORPHOLOGY; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; PHENOTYPE; RCAN1 GENE; SEPTIN 4 GENE; SOD1 GENE; SYMPTOM; ADULT; ANIMAL; BRAIN; DEGENERATIVE DISEASE; DISEASE MODEL; GENETICS; GROWTH, DEVELOPMENT AND AGING; MIDDLE AGED; MOUSE; PATHOLOGY; TRANSGENIC MOUSE;

ADULT; ALZHEIMER DISEASE; ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; DOWN SYNDROME; GENES; HUMANS; MICE; MICE, TRANSGENIC; MIDDLE AGED; NEURODEGENERATIVE DISEASES;

EID: 77954330733     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710791556159     Document Type: Article

References (117)

1. Glasson, E.J.; Sullivan, S.G.; Hussain, R.; Petterson, B.A.; Montgomery, P.D.; Bittles, A.H. Comparative survival advantage of males with Down syndrome. Am. J. Hum. Biol., 2003, 15, 192-195.
2. Bittles, A.H.; Bower, C.; Hussain, R.; Glasson, E.J. The four ages of Down syndrome. Eur. J. Public Health, 2007, 17, 221-225.
3. Penrose, L.S. The incidence of mongolism in the general population. J. Ment. Sci., 1949, 95, 685-688.
4. Bittles, A.H.; Glasson, E.J. Clinical, social, and ethical implications of changing life expectancy in Down syndrome. Dev. Med. Child. Neurol., 2004, 46, 282-286.
5. Glasson, E.J.; Sullivan, S.G.; Hussain, R.; Petterson, B.A.; Montgomery, P.D.; Bittles, A.H. The changing survival profile of people with Down's syndrome: implications for genetic counselling. Clin. Genet., 2002, 62, 390-393.
6. Yang, Q.; Rasmussen, S.A.; Friedman, J.M. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet, 2002, 359, 1019-1025.
7. Raji, N.S.; Rao, K.S. Trisomy 21 and accelerated aging: DNA- repair parameters in peripheral lymphocytes of Down's syndrome patients. Mech. Ageing Dev., 1998, 100, 85-101.
8. Nakamura, E.; Tanaka, S. Biological ages of adult men and women with Down's syndrome and its changes with aging. Mech. Ageing Dev., 1998, 105, 89-103.
9. Hill, D.A.; Gridley, G.; Cnattingius, S.; Mellemkjaer, L.; Linet, M.; Adami, H.O.; Olsen, J.H.; Nyren, O.; Fraumeni, J.F., Jr. Mortality and cancer incidence among individuals with Down syndrome. Arch. Intern. Med., 2003, 163, 705-711.
10. Janicki, M.P.; Dalton, A.J.; Henderson, C.M.; Davidson, P.W. Mortality and morbidity among older adults with intellectual disability: health services considerations. Disabil. Rehabil., 1999, 21, 284-294.
11. Alexander, G.E.; Saunders, A.M.; Szczepanik, J.; Strassburger, T.L.; Pietrini, P.; Dani, A.; Furey, M.L.; Mentis, M.J.; Roses, A.D.; Rapoport, S.I.; Schapiro, M.B. Relation of age and apolipoprotein E to cognitive function in Down syndrome adults. Neuroreport, 1997, 8, 1835-1840.
12. Schapiro, M.B.; Azari, N.P.; Grady, C.L.; Haxby, J.V.; Horwitz, B. Down syndrome: differentiating mental retardation and dementia with brain imaging techniques. Prog. Clin. Biol. Res., 1992, 379, 103-122.
13. Zigman, W.B.; Lott, I.T. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment. Retard. Dev. Disabil. Res. Rev., 2007, 13, 237-46.
14. Bush, A.; Beail, N. Risk factors for dementia in people with down syndrome: issues in assessment and diagnosis. Am. J. Ment. Retard., 2004, 109, 83-97.
15. Aylward, E.H.; Burt, D.B.; Thorpe, L.U.; Lai, F.; Dalton, A. Diagnosis of dementia in individuals with intellectual disability. J. Intellect. Disabil. Res., 1997, 41, 152-164.
16. 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.
17. Devenny, D.A.; Krinsky-Mchale, S.J.; Sersen, G.; Silverman, W.P. Sequence of cognitive decline in dementia in adults with Down's syndrome. J. Intellect. Disabil. Res., 2000, 44, 654-665.
18. Schupf, N.; Pang, D.; Patel, B.N.; Silverman, W.; Schubert, R.; Lai, F.; Kline, J.K.; Stern, Y.; Ferin, M.; Tycko, B.; Mayeux, R. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann. Neurol., 2003, 54, 433-438.
19. Schupf, N.; Winsten, S.; Patel, B.; Pang, D.; Ferin, M.; Zigman, W.B.; Silverman, W.; Mayeux, R. Bioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome. Neurosci. Lett., 2006, 406, 298-302.
20. Devenny, D.A.; Silverman, W.P.; Hill, A.L.; Jenkins, E.; Sersen, E.A.; Wisniewski, K.E. Normal ageing in adults with Down's syndrome: a longitudinal study. J. Intellect. Disabil. Res., 1996, 40, 208-221.
21. Schupf, N.; Sergievsky, G.H. Genetic and host factors for dementia in Down's syndrome. Br. J. Psychiatry, 2002, 180, 405-410.
22. Jernigan, T.L.; Bellugi, U.; Sowell, E.; Doherty, S.; Hesselink, J.R. Cerebral morphologic distinctions between Williams and Down syndromes. Arch. Neurol., 1993, 50, 186-191.
23. Pinter, J.D.; Eliez, S.; Schmitt, J.E.; Capone, G.T.; Reiss, A.L. Neuroanatomy of Down's syndrome: a high-resolution MRI study. Am. J. Psychiatry, 2001, 158, 1659-1665.
24. Becker, L.; Mito, T.; Takashima, S.; Onodera, K. Growth and development of the brain in Down syndrome. Prog. Clin. Biol. Res., 1991, 373, 133-152.
25. Coyle, J.T.; Oster-Granite, M.L.; Gearhart, J.D. The neurobiologic consequences of Down syndrome. Brain. Res. Bull., 1986, 16, 773-787.
26. Kesslak, J.P.; Nagata, S.F.; Lott, I.; Nalcioglu, O. Magnetic resonance imaging analysis of age-related changes in the brains of individuals with Down's syndrome. Neurology, 1994, 44, 1039-1045.
27. Wisniewski, K.E. Down syndrome children often have brain with maturation delay, retardation of growth, and cortical dysgenesis. Am. J. Med. Genet. Suppl., 1990, 7, 274-281.
28. Raz, N.; Torres, I.J.; Briggs, S.D.; Spencer, W.D.; Thornton, A.E.; Loken, W.J.; Gunning, F.M.; Mcquain, J.D.; Driesen, N.R.; Acker, J.D. Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry. Neurology, 1995, 45, 356-366.
29. Dierssen, M.; Herault, Y.; Estivill, X. Aneuploidy: from a physiological mechanism of variance to Down syndrome. Physiol. Rev., 2009, 89, 887-920.
30. Teipel, S.J.; Hampel, H. Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer's disease. Behav. Genet., 2006, 36, 405-415.
31. Beacher, F.; Daly, E.; Simmons, A.; Prasher, V.; Morris, R.; Robinson, C.; Lovestone, S.; Murphy, K.; Murphy, D.G. Brain anatomy and ageing in non-demented adults with Down's syndrome: an in vivo MRI study. Psychol. Med., 2009, 1-9.
32. Fox, N.C.; Crum, W.R.; Scahill, R.I.; Stevens, J.M.; Janssen, J.C.; Rossor, M.N. Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images. Lancet, 2001, 358, 201-205.
33. Karas, G.B.; Scheltens, P.; Rombouts, S.A.; Visser, P.J.; Van Schijndel, R.A.; Fox, N.C.; Barkhof, F. Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease. Neuroimage, 2004, 23, 708-716.
34. Wisniewski, K.; Howe, J.; Williams, D.G.; Wisniewski, H.M. Precocious aging and dementia in patients with Down's syndrome. Biol. Psychiatry, 1978, 13, 619-627.
35. Wisniewski, K.E.; Wisniewski, H.M.; Wen, G.Y. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann. Neurol., 1985, 17, 278-282.
36. Mann, D.M.; Esiri, M.M. 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.
37. Nistor, M.; Don, M.; Parekh, M.; Sarsoza, F.; Goodus, M.; Lopez, G.E.; Kawas, C.; Leverenz, J.; Doran, E.; Lott, I.T.; Hill, M.; Head, E. Alpha- and beta-secretase activity as a function of age and beta- amyloid in Down syndrome and normal brain. Neurobiol. Aging, 2007, 28, 1493-1506.
38. Rovelet-Lecrux, A.; Hannequin, D.; Raux, G.; Le Meur, N.; Laquerriere, A.; Vital, A.; Dumanchin, C.; Feuillette, S.; Brice, A.; Vercelletto, M.; Dubas, F.; Frebourg, T.; Campion, D. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat. Genet., 2006, 38, 24-26.
39. Hof, P.R.; Bouras, C.; Perl, D.P.; Sparks, D.L.; Mehta, N.; Morrison, J.H. 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.
40. Azizeh, B.Y.; Head, E.; Ibrahim, M.A.; Torp, R.; Tenner, A.J.; Kim, R.C.; Lott, I.T.; Cotman, C.W. Molecular dating of senile plaques in the brains of individuals with Down syndrome and in aged dogs. Exp. Neurol., 2000, 163, 111-122.
41. Leverenz, J.B.; Raskind, M.A. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp. Neurol., 1998, 150, 296-304.
42. Flament, S.; Delacourte, A.; Mann, D.M. Phosphorylation of Tau proteins: a major event during the process of neurofibrillary degeneration: a comparative study between Alzheimer's disease and Down's syndrome. Brain Res., 1990, 516, 15-19.
43. Grundke-Iqbal, I.; Iqbal, K.; Quinlan, M.; Tung, Y.C.; Zaidi, M.S.; Wisniewski, H.M. Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J. Biol. Chem., 1986, 261, 6084-6089.
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. USA, 1986, 83, 4913-4917.
45. Liang, Z.; Liu, F.; Iqbal, K.; Grundke-Iqbal, I.; Wegiel, J.; Gong, C.X. Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome. J. Alzheimers Dis., 2008, 13, 295-302.
46. Murphy, G.M., Jr.; Eng, L.F.; Ellis, W.G.; Perry, G.; Meissner, L.C.; Tinklenberg, J.R. Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease. Brain. Res., 1990, 537, 102-108.
47. Margallo-Lana, M.L.; Moore, P.B.; Kay, D.W.; Perry, R.H.; Reid, B.E.; Berney, T.P.; Tyrer, S.P. 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.
48. Jones, E.L.; Margallo-Lana, M.; Prasher, V.P.; Ballard, C.G. The extended tau haplotype and the age of onset of dementia in Down syndrome. Dement. Geriatr. Cogn. Disord., 2008, 26, 199-202.
49. Yates, C.M.; Simpson, J.; Gordon, A. 5-Hydroxytryptamine and dopamine in pre-senile and senile Alzheimer-type dementia. Biochem. Soc. Trans., 1990, 18, 422-423.
50. Casanova, M.F.; Walker, L.C.; Whitehouse, P.J.; Price, D.L. Abnormalities of the nucleus basalis in Down's syndrome. Ann. Neurol., 1985, 18, 310-313.
51. Head, E.; Garzon-Rodriguez, W.; Johnson, J.K.; Lott, I.T.; Cotman, C.W.; Glabe, C. Oxidation of Abeta and plaque biogenesis in Alzheimer's disease and Down syndrome. Neurobiol. Dis., 2001, 8, 792-806.
52. Nardone, R.; Marth, R.; Ausserer, H.; Bratti, A.; Tezzon, F. Reduced short latency afferent inhibition in patients with Down syndrome and Alzheimer-type dementia. Clin. Neurophysiol., 2006, 117, 2204-2210.
53. Kishnani, P.S.; Sullivan, J.A.; Walter, B.K.; Spiridigliozzi, G.A.; Doraiswamy, P.M.; Krishnan, K.R. Cholinergic therapy for Down's syndrome. Lancet, 1999, 353, 1064-1065.
54. Mufson, E.J.; Ma, S.Y.; Cochran, E.J.; Bennett, D.A.; Beckett, L.A.; Jaffar, S.; Saragovi, H.U.; Kordower, J.H. Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease. J. Comp. Neurol., 2000, 427, 19-30.
55. Sendera, T.J.; Ma, S.Y.; Jaffar, S.; Kozlowski, P.B.; Kordower, J.H.; Mawal, Y.; Saragovi, H.U.; Mufson, E.J. Reduction in TrkA- immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome. J. Neurochem., 2000, 74, 1185-1196.
56. Isacson, O.; Seo, H.; Lin, L.; Albeck, D.; Granholm, A.C. Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh. Trends Neurosci., 2002, 25, 79-84.
57. Opazo, P.; Saud, K.; De Saint Pierre, M.; Cardenas, A.M.; Allen, D.D.; Segura-Aguilar, J.; Caviedes, R.; Caviedes, P. Knockdown of amyloid precursor protein normalizes cholinergic function in a cell line derived from the cerebral cortex of a trisomy 16 mouse: An animal model of down syndrome. J. Neurosci. Res., 2006, 84, 1303-1310.
58. Wenk, G.L.; Rosi, S.; Mcgann, K.; Hauss-Wegrzyniak, B. A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat. Eur. J. Pharmacol., 2002, 453, 319-324.
59. Pallardo, F.V.; Degan, P.; D'ischia, M.; Kelly, F.J.; Zatterale, A.; Calzone, R.; Castello, G.; Fernandez-Delgado, R.; Dunster, C.; Lloret, A.; Manini, P.; Pisanti, M.A.; Vuttariello, E.; Pagano, G. Multiple evidence for an early age pro-oxidant state in Down Syndrome patients. Biogerontology, 2006, 7, 211-220.
60. Lott, I.T.; Head, E. Down syndrome and Alzheimer's disease: a link between development and aging. Ment. Retard. Dev. Disabil. Res. Rev., 2001, 7, 172-178.
61. Amieva, H.; Jacqmin-Gadda, H.; Orgogozo, J.M.; Le Carret, N.; Helmer, C.; Letenneur, L.; Barberger-Gateau, P.; Fabrigoule, C.; Dartigues, J.F. The 9 year cognitive decline before dementia of the Alzheimer type: a prospective population-based study. Brain, 2005, 128, 1093-1101.
62. Elias, M.F.; Beiser, A.; Wolf, P.A.; Au, R.; White, R.F.; D'agostino, R.B. The preclinical phase of alzheimer disease: A 22- year prospective study of the Framingham Cohort. Arch. Neurol., 2000, 57, 808-813.
63. Small, B.J.; Fratiglioni, L.; Viitanen, M.; Winblad, B.; Backman, L. The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample. Arch. Neurol., 2000, 57, 839-844.
64. Head, E.; Lott, I.T.; Patterson, D.; Doran, E.; Haier, R.J. Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention. J. Alzheimers Dis., 2007, 11, 61-76.
65. Haier, R.J.; Head, K.; Head, E.; Lott, I.T. Neuroimaging of individuals with Down's syndrome at-risk for dementia: evidence for possible compensatory events. Neuroimage, 2008, 39, 1324-1332.
66. Altafaj, X.; Dierssen, M.; Baamonde, C.; Marti, E.; Visa, J.; Guimera, J.; Oset, M.; Gonzalez, J.R.; Florez, J.; Fillat, C.; Estivill, X. Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum. Mol. Genet., 2001, 10, 1915-1923.
67. Kimura, R.; Kamino, K.; Yamamoto, M.; Nuripa, A.; Kida, T.; Kazui, H.; Hashimoto, R.; Tanaka, T.; Kudo, T.; Yamagata, H.; Tabara, Y.; Miki, T.; Akatsu, H.; Kosaka, K.; Funakoshi, E.; Nishitomi, K.; Sakaguchi, G.; Kato, A.; Hattori, H.; Uema, T.; Takeda, M. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease. Hum. Mol. Genet., 2007, 16, 15-23.
68. Wegiel, J.; Dowjat, K.; Kaczmarski, W.; Kuchna, I.; Nowicki, K.; Frackowiak, J.; Mazur Kolecka, B.; Wegiel, J.; Silverman, W.P.; Reisberg, B.; Deleon, M.; Wisniewski, T.; Gong, C.X.; Liu, F.; Adayev, T.; Chen-Hwang, M.C.; Hwang, Y.W. The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome. Acta Neuropathol., 2008, 116, 391-407.
69. Ryoo, S.R.; Cho, H.J.; Lee, H.W.; Jeong, H.K.; Radnaabazar, C.; Kim, Y.S.; Kim, M.J.; Son, M.Y.; Seo, H.; Chung, S.H.; Song, W.J. Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer's disease. J. Neurochem., 2008, 104, 1333-1344.
70. Woods, Y.L.; Cohen, P.; Becker, W.; Jakes, R.; Goedert, M.; Wang, X.; Proud, C.G. The kinase DYRK phosphorylates protein- synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem. J., 2001, 355, 609-615.
71. Ferrer, I.; Barrachina, M.; Puig, B.; Martinez De Lagran, M.; Marti, E.; Avila, J.; Dierssen, M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol. Dis., 2005, 20, 392-400.
72. Sitz, J.H.; Baumgartel, K.; Hammerle, B.; Papadopoulos, C.; Hekerman, P.; Tejedor, F.J.; Becker, W.; Lutz, B. The Down syndrome candidate dual-specificity tyrosine phosphorylation- regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience, 2008, 157, 596-605.
73. Ermak, G.; Harris, C.D.; Battocchio, D.; Davies, K.J. RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3beta. FEBS J., 2006, 273, 2100-2109.
74. Porta, S.; Marti, E.; De La Luna, S.; Arbones, M.L. Differential expression of members of the RCAN family of calcineurin regulators suggests selective functions for these proteins in the brain. Eur. J. Neurosci., 2007, 26, 1213-1226.
75. Keating, D.J.; Dubach, D.; Zanin, M.P.; Yu, Y.; Martin, K.; Zhao, Y.F.; Chen, C.; Porta, S.; Arbones, M.L.; Mittaz, L.; Pritchard, M.A. DSCR1/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: implications for Down syndrome and Alzheimer's disease. Hum. Mol. Genet., 2008, 17, 1020-1030.
76. Cheon, M.S.; Dierssen, M.; Kim, S.H.; Lubec, G. Protein expression of BACE1, BACE2 and APP in Down syndrome brains. Amino Acids, 2008, 35, 339-343.
77. 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.
78. Azkona, G.; Amador-Arjona, A.; Obradors-Tarrago, C.; Varea, E.; Arque, G.; Pinacho, R.; Fillat, C.; De La Luna, S.; Estivill, X.; Dierssen, M. Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2. Genes Brain Behav., 2009 [Epub ahead of print].
79. Brooksbank, B.W.; Balazs, R. Superoxide dismutase and lipoperoxidation in Down's syndrome fetal brain. Lancet, 1983, 1, 881-882.
80. Seregaza, Z.; Roubertoux, P.L.; Jamon, M.; Soumireu-Mourat, B. Mouse models of cognitive disorders in trisomy 21: a review. Behav. Genet., 2006, 36, 387-404.
81. Davisson, M.T.; Schmidt, C.; Akeson, E.C. Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog. Clin. Biol. Res., 1990, 360, 263-280.
82. Cooper, J.D.; Salehi, A.; Delcroix, J.D.; Howe, C.L.; Belichenko, P.V.; Chua-Couzens, J.; Kilbridge, J.F.; Carlson, E.J.; Epstein, C.J.; Mobley, W.C. 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, 2001, 98, 10439-10444.
83. Granholm, A.C.; Sanders, L.A.; Crnic, L.S. Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome. Exp. Neurol., 2000, 161, 647-663.
84. Seo, H.; Isacson, O. Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice. Exp. Neurol., 2005, 193, 469-480.
85. Hefti, F.; Will, B. Nerve growth factor is a neurotrophic factor for forebrain cholinergic neurons; implications for Alzheimer's disease. J. Neural Transm. Suppl., 1987, 24, 309-315.
86. Hunter, C.L.; Isacson, O.; Nelson, M.; Bimonte-Nelson, H.; Seo, H.; Lin, L.; Ford, K.; Kindy, M.S.; Granholm, A.C. Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down's syndrome. Neurosci. Res., 2003, 45, 437-445.
87. Salehi, A.; Delcroix, J.D.; Belichenko, P.V.; Zhan, K.; Wu, C.; Valletta, J.S.; Takimoto-Kimura, R.; Kleschevnikov, A.M.; Sambamurti, K.; Chung, P.P.; Xia, W.; Villar, A.; Campbell, W.A.; Kulnane, L.S.; Nixon, R.A.; Lamb, B.T.; Epstein, C.J.; Stokin, G.B.; Goldstein, L.S.; Mobley, W.C. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron, 2006, 51, 29-42.
88. Cataldo, A.M.; Petanceska, S.; Peterhoff, C.M.; Terio, N.B.; Epstein, C.J.; Villar, A.; Carlson, E.J.; Staufenbiel, M.; Nixon, R.A. App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. J. Neurosci., 2003, 23, 6788-6792.
89. Choi, J.H.; Berger, J.D.; Mazzella, M.J.; Morales-Corraliza, J.; Cataldo, A.M.; Nixon, R.A.; Ginsberg, S.D.; Levy, E.; Mathews, P.M. Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model. J. Neurochem., 2009, 110, 1818-1827.
90. Holtzman, D.M.; Santucci, D.; Kilbridge, J.; Chua-Couzens, J.; Fontana, D.J.; Daniels, S.E.; Johnson, R.M.; Chen, K.; Sun, Y.; Carlson, E.; Alleva, E.; Epstein, C.J.; Mobley, W.C. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc. Natl. Acad. Sci. USA, 1996, 93, 13333-13338.
91. Liu, F.; Liang, Z.; Wegiel, J.; Hwang, Y.W.; Iqbal, K.; Grundke- Iqbal, I.; Ramakrishna, N.; Gong, C.X. Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. FASEB J., 2008, 22, 3224-3233.
92. Sago, H.; Carlson, E.J.; Smith, D.J.; Kilbridge, J.; Rubin, E.M.; Mobley, W.C.; Epstein, C.J.; Huang, T.T. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc. Natl. Acad. Sci. USA, 1998, 95, 6256-6261.
93. Richtsmeier, J.T.; Zumwalt, A.; Carlson, E.J.; Epstein, C.J.; Reeves, R.H. Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome. Am. J. Med. Genet., 2002, 107, 317-324.
94. Olson, L.E.; Roper, R.J.; Baxter, L.L.; Carlson, E.J.; Epstein, C.J.; Reeves, R.H. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev. Dyn., 2004, 230, 581-589.
95. Shukkur, E.A.; Shimohata, A.; Akagi, T.; Yu, W.; Yamaguchi, M.; Murayama, M.; Chui, D.; Takeuchi, T.; Amano, K.; Subramhanya, K.H.; Hashikawa, T.; Sago, H.; Epstein, C.J.; Takashima, A.; Yamakawa, K. Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome. Hum. Mol. Genet., 2006, 15, 2752-2762.
96. Olson, L.E.; Roper, R.J.; Sengstaken, C.L.; Peterson, E.A.; Aquino, V.; Galdzicki, Z.; Siarey, R.; Pletnikov, M.; Moran, T.H.; Reeves, R.H. Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. Hum. Mol. Genet., 2007, 16, 774-782.
97. Belichenko, N.P.; Belichenko, P.V.; Kleschevnikov, A.M.; Salehi, A.; Reeves, R.H.; Mobley, W.C. The Down syndrome critical region is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome. J. Neurosci., 2009, 29, 5938-5948.
98. Bossy-Wetzel, E.; Schwarzenbacher, R.; Lipton, S.A. Molecular pathways to neurodegeneration. Nat. Med., 2004, 10(Suppl), S2-S9.
99. Simon, A.M.; Schiapparelli, L.; Salazar-Colocho, P.; Cuadrado- Tejedor, M.; Escribano, L.; Lopez De Maturana, R.; Del Rio, J.; Perez-Mediavilla, A.; Frechilla, D. Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol. Dis., 2009, 33, 369-378.
100. Ghosal, K.; Vogt, D.L.; Liang, M.; Shen, Y.; Lamb, B.T.; Pimplikar, S.W. Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain. Proc. Natl. Acad. Sci. USA, 2009, 106, 18367-18372.
101. Prasher, V.P.; Farrer, M.J.; Kessling, A.M.; Fisher, E.M.; West, R.J.; Barber, P.C.; Butler, A.C. Molecular mapping of Alzheimer- type dementia in Down's syndrome. Ann. Neurol., 1998, 43, 380-383.
102. Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc. Natl. Acad. Sci. USA, 1987, 84, 8044-8048.
103. Yarom, R.; Sapoznikov, D.; Havivi, Y.; Avraham, K.B.; Schickler, M.; Groner, Y. Premature aging changes in neuromuscular junctions of transgenic mice with an extra human CuZnSOD gene: a model for tongue pathology in Down's syndrome. J. Neurol. Sci., 1988, 88, 41-53.
104. Ceballos-Picot, I.; Nicole, A.; Briand, P.; Grimber, G.; Delacourte, A.; Defossez, A.; Javoy-Agid, F.; Lafon, M.; Blouin, J.L.; Sinet, P.M. Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effects in Down's syndrome. Brain. Res., 1991, 552, 198-214.
105. Bar-Peled, O.; Korkotian, E.; Segal, M.; Groner, Y. Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons. Proc Natl. Acad. Sci. USA, 1996, 93, 8530-8535.
106. Harris-Cerruti, C.; Kamsler, A.; Kaplan, B.; Lamb, B.; Segal, M.; Groner, Y. Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein [correction]. Eur. J. Neurosci., 2004, 19, 1174-1190.
107. Borg, J.; Chereul, E. Differential MRI patterns of brain atrophy in double or single transgenic mice for APP and/or SOD. J. Neurosci. Res., 2008, 86, 3275-3284.
108. Smith, D.J.; Stevens, M.E.; Sudanagunta, S.P.; Bronson, R.T.; Makhinson, M.; Watabe, A.M.; O'dell, T.J.; Fung, J.; Weier, H.U.; Cheng, J.F.; Rubin, E.M. Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Nat. Genet., 1997, 16, 28-36.
109. Ahn, K.J.; Jeong, H.K.; Choi, H.S.; Ryoo, S.R.; Kim, Y.J.; Goo, J.S.; Choi, S.Y.; Han, J.S.; Ha, I.; Song, W.J. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol. Dis., 2006, 22, 463-472.
110. Ryoo, S.R.; Jeong, H.K.; Radnaabazar, C.; Yoo, J.J.; Cho, H.J.; Lee, H.W.; Kim, I.S.; Cheon, Y.H.; Ahn, Y.S.; Chung, S.H.; Song, W.J. DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease. J. Biol. Chem., 2007, 282, 34850-34857.
111. Bucci, C.; Parton, R.G.; Mather, I.H.; Stunnenberg, H.; Simons, K.; Hoflack, B.; Zerial, M. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell, 1992, 70, 715-728.
112. Cataldo, A.M.; Peterhoff, C.M.; Troncoso, J.C.; Gomez-Isla, T.; Hyman, B.T.; Nixon, R.A. 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.
113. Chang, K.T.; Min, K.T. Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function. Nat. Neurosci., 2005, 8, 1577-1585.
114. Hoeffer, C.A.; Dey, A.; Sachan, N.; Wong, H.; Patterson, R.J.; Shelton, J.M.; Richardson, J.A.; Klann, E.; Rothermel, B.A. The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling. J. Neurosci., 2007, 27, 13161-13172.
115. Hunter, C.L.; Bachman, D.; Granholm, A.C. Minocycline prevents cholinergic loss in a mouse model of Down's syndrome. Ann. Neurol., 2004, 56, 675-688.
116. Granholm, A.C.; Ford, K.A.; Hyde, L.A.; Bimonte, H.A.; Hunter, C.L.; Nelson, M.; Albeck, D.; Sanders, L.A.; Mufson, E.J.; Crnic, L.S. Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome. Physiol. Behav., 2002, 77, 371-385.
117. Lockrow, J.; Prakasam, A.; Huang, P.; Bimonte-Nelson, H.; Sambamurti, K.; Granholm, A.C. Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model. Exp. Neurol., 2009, 216, 278-289.