Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer's disease

Acta Neurobiologiae Experimentalis

Volumn 69, Issue 2, 2009, Pages 232-253

  Z̊ekanowski, Cezary ^a   Wojda, Urszula ^b  

^a MOSSAKOWSKI MEDICAL RESEARCH CENTRE   (Poland)

^b INTERNATIONAL INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Poland)

Author keywords

Alzheimer's disease; Aneuploidy; Apoptosis; Cell cycle; Chromosome missegregation; DNA damage; DNA repair; Down's syndrome; Genome instability; Neuron; Oxidative stress; Presenilin

Indexed keywords

AMYLOID BETA PROTEIN; TAU PROTEIN;

ALZHEIMER DISEASE; ANEUPLOIDY; ANIMAL; BRAIN; CELL CYCLE; CHROMOSOME; GENETIC PREDISPOSITION; GENETICS; HUMAN; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANEUPLOIDY; ANIMALS; BRAIN; CELL CYCLE; CHROMOSOMES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; TAU PROTEINS;

EID: 70349258199     PISSN: 00651400     EISSN: 00651400     Source Type: Journal    
DOI: None     Document Type: Review

References (195)

1. Alexson TO, Hitoshi S, Coles BL, Bernstein A, van der Kooy D (2006) Notch signaling is required to maintain all neural stem cell populations - irrespective of spatial or temporal niche. Dev Neurosci 28: 34-48.
2. Alliegro MC, Alliegro MA (2008) Centrosomal RNA correlates with intron-poor nuclear genes in Spisula oocytes. Proc Natl Acad Sci U S A 105: 6993-6997.
3. An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Iqbal IG, Winblad B, Pei JJ (2003) Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. Am J Pathol 163: 591-607.
4. Andorfer C, Acker CM, Kress Y, Hof PR, Duff K, Davies P (2005) Cell-Cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25: 5446-5454.
5. Appert-Collin A, Hugel B, Levy R, Niederhoffer N, Coupin G, Lombard Y, André P, Poindron P, Gies JP (2006) Cyclin dependent kinase inhibitors prevent apoptosis of postmitotic mouse motoneurons. Life Sci 79: 484-490.
6. Arendt, T (1993) Neuronal dedifferentiation and degeneration in Alzheimer's disease. Biol.Chem. Hoppe-Seyler 374: 911-912.
7. Arendt T, Brückner MK, Gertz HJ, Marcova L (1998) Cortical distribution of neurofibrillary tangles in Alzheimer's disease matches the pattern of neurons that retain their capacity of plastic remodelling in the adult brain. Neuroscience 83: 991-1002.
8. Arendt T (2003) Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the "Dr. Jekyll and Mr. Hyde concept" of Alzheimer's disease or the yin and yang of neuroplasticity. Prog Neurobiol 71: 83-248.
9. Arendt T, Brückner MK (2007) Linking cell-cycle dysfunction in Alzheimer's disease to a failure of synaptic plasticity. Biochim Biophys Acta 1772: 413-421.
10. Avramopoulos D, Mikkelsen M, Vassilopoulos D, Grigoriadou M, Petersen MB (1996) Apolipoprotein E allele distribution in parents with Down's syndrome children. Lancet 347: 862-865.
11. Bajic VP, Spremo-Potparevic B, Zivkovic L, Djelic N, Smith MA (2008) Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics? Biosci Hypoth 1: 156-161.
12. Baki L, Neve RL, Shao Z, Shioi J, Georgakopoulos A, Robakis NK (2008) Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling. J Neurosci 28: 483-490.
13. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama-Sosa M, Neve R, Robakis NK (2004) PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J 23: 2586-2596.
14. Balastik M, Lim J, Pastorino L, Lu KP (2007) Pin1 in Alzheimer's disease: Multiple substrates, one regulatory mechanism? Biochim Biophys Acta 1772: 422-442.
15. Baas PW (1999) Microtubules and neuronal polarity: lessons from mitosis. Neuron 22: 23-31.
16. Battaglia F, Quartarone A, Rizzo V, Ghilardi MF, Di Rocco A, Tortorella G, Girlanda P (2008) Early impairment of synaptic plasticity in patients with Down's syndrome. Neurobiol Aging 29: 1272-1275.
17. Bertram L, Tanzi RE (2008) Thirty years of Alzheimer's disease genetics: the implications of systematic metaanalyses. Nat Rev Neurosci 9: 768-778.
18. Blom ES, Viswanathan J, Kilander L, Helisalmi S, Soininen H, Lannfelt L, Ingelsson M, Glaser A, Hiltunen M (2008) Low prevalence of APP duplications in Swedish and Finnish patients with early-onset Alzheimer's disease. Eur J Hum Genet 16: 171-175.
19. Boeras DI, Granic A, Padmanabhan J, Crespo NC, Rojiani AM, Potter H (2008) Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy. Neurobiol Aging 29: 319-328.
20. Buckton KE, Whalley LJ, Lee M (1983) Chromosome changes in Alzheimer's presenile dementia. J Med Genet 20: 46-51.
21. Busciglio J, Yankner BA (1997) Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. Nature 378: 776-779.
22. Caltagarone J, Jing Z, Bowser R (2007) Focal adhesions regulate Aβ signaling and cell death in Alzheimer's disease. Biochim Biophys Acta 1772: 438-445.
23. Cenini G, Sultana R, Memo M, Butterfield DA (2008) Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease. J Cell Mol Med 12: 987-994.
24. Checler F, Sunyach C, Pardossi-Piquard R, Sévalle J, Vincent B, Kawarai T, Girardot N, St George-Hyslop P, da Costa CA (2007) The gamma/epsilon-secretase-derived APP intracellular domain fragments regulate p53. Curr Alzheimer Res 4: 423-426.
25. Chee FC, Mudher A, Cuttle MF, Newman TA, MacKay D, Lovestone S, Shepherd D (2005) Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions. Neurobiol Dis 20: 918-928.
26. Chen P, Zindy F, Abdala C, Liu F, Li X, Roussel MF, Segil N (2003) Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nat Cell Biol 5: 422-426.
27. Chevallier NL, Soriano S, Kang DE Masliah E, Hu G, Koo EH (2005) Perturbed neurogenesis in the adult hippocampus associated with presenilin 1 A246E mutation. Am J Pathol 167: 151-159.
28. Chiang PK, Lam MA, Luo Y (2008) The many faces of amyloid beta in Alzheimer's disease. Curr Mol Med 8: 580-584.
29. Contestabile A, Fila T, Ceccarelli C, Bonasoni P, Bonapace L, Santini D, Bartesaghi R, Ciani E (2007) Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice. Hippocampus 17: 665-678.
30. Copani A, Caraci F, Hoozemans JM, Calafiore M, Sortino A (2007) The nature of the cell cycle in neurons: Focus on a "non-canonical" pathway of DNA replication causally related to death. Biochim Biophys Acta 1772: 409-412.
31. Cruts M, Van Broeckhoven C (1998) Molecular genetics of Alzheimer's disease. Ann Med 30: 60-65.
32. Dickey CA, Loring JF, Montgomery J, Gordon MN, Eastman PS, Morgan D (2003) Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J Neurosci 23: 5219-5226.
33. Dehmelt L, Halpain S (2005) The MAP2/Tau family of microtubule-associated pr teins. Genome Biol 6: 204.
34. Delobel P, Lavenir I, Ghetti B, Holzer M, Goedert M (2006) Cell-cycle markers in a transgenic mouse model of human tauopathy: increased levels of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. Am J Pathol 168: 878-887.
35. Dranovsky A, Oxberry W, Lyubsky S, Goldgaber D (1996) APP is associated with mitotic centrosomes and a distinct cytoplasmic network which colocalizes with depolymerized tubulin. Neurobiol Aging 17 (Suppl. 1): S196.
36. Ezquerra M, Ballesta F, Queralt R, Aledo R, Gómez D, Guitart M, Egozcue J, Ascaso C, Oliva R (1998) Apolipoprotein E epsilon 4 alleles and meiotic origin of non-disjunction in Down syndrome children and in their corresponding fathers and mothers. Neurosci Lett 248: 1-4.
37. Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2006) DNA Repair and Mutagenesis. Part 3. (2nd ed.). ASM Press, Herndon, VA.
38. Galli C, Piccini A, Ciotti MT, Castellani L, Calissano P, Zaccheo D, Tabaton M (1998) Increased amyloidogenic secretion in cerebellar granule cells undergoing apoptosis. Proc Natl Acad Sci U S A 95: 1247-1252.
39. Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL (2006) Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 63: 168-174.
40. Geller LN, Potter H (1999) Chromosome mis-segregation and trisomy 21 mosaicism in Alzheimer's disease. Neurobiol Dis 6: 167-179.
41. Gent van DC, Hoeijmakes JH, Kanaar R (2001) Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet 2: 196-206.
42. Giménez-Llort L, Blázquez G, Cañete T, Johansson B, Oddo S, Tobeña A, LaFerla FM, Fernández-Teruel A (2007) Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: a role for intraneuronal amyloid. Neurosci Biobehav Rev 31: 125-147.
43. Goodwin B, Padmanabhan J, Granic A, Owens C, CrespoN, Potter H (2008) Inhibition of gamma-secretase activity induces cell cycle defects and chromosome missegregation. Alzheimers Dement 4 (Suppl. 1): T614.
44. Harbour JW, Dean DC (2000) Rb function in cell-cycle regulation and apoptosis, Nat Cell Biol 2: E65-E67.
45. Hardy OJ, Goate A, Owen M, Rossor M (1989) Presenile dementia associated with mosaic trisomy 21 in a patient with a Down syndrome child. Lancet 8665: 743.
46. Heintz N (1993) Cell death and the cell cycle: a relationship between transformation and neurodegeneration? Trends Biochem Sci 18: 157-159.
47. Herrup K, Arendt T (2002) Re-expression of cell cycle proteins induce neuronal cell death during Alzheimer's disease. J Alzheimers Dis 4: 243-247.
48. Herrup K, Neve R, Ackerman SL, Copani A (2004) Divide and die: cell cycle events as triggers of nerve cell death. J Neurosci 24: 9232-9239.
49. Herrup K, Cohen M, Chen J, Yang Y, Lerner A (2008) Cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer pathology. Alzheimers Dement 4 (Suppl. 1): T614.
50. Heston LL, Mastri AR, Anderson VE, White J (1981) Dementia of the Alzheimer type. Arch Gen Psychiatr 38: 1084-1090.
51. Heyman A, Wilkinson W, Hurwitz B, Schmechel D, Sigmon AH, Weinberg T, Helms MJ, Swift M (1983) Alzheimer's disease genetic aspects and associated clinical disorders. Ann Neurol 14: 507-515.
52. Higuchi Y (2003) Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol 66: 1527-1535.
53. Honda T, Nihonmatsu N, Yasutake K, Ohtake A, Sato K, Tanaka S, Murayama O, Murayama M, Takashima A (2000) Familial Alzheimer's disease-associated mutations block translocation of full-length presenilin 1 to the nuclear envelope. Neurosci Res 37: 101-111.
54. Illenberger S, Zheng-Fischhöfer Q, Preuss U, Stamer K, Baumann K, Trinczek B, Biernat J, Godemann R, Mandelkow EM, Mandelkow E (1998) The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol Biol Cell 9: 1495-1512.
55. Iourov IY, Liehr T, Vorsanova SG, Kolotii AD, Yurov YB (2006) Visualization of interphase chromosomes in postmitotic cells of the human brain by multicolour banding (MCB). Chromosome Res 14: 223-229.
56. Iourov IY, Liehr T, Vorsanova SG, Yurov YB (2007) Interphase chromosome-specific multicolor banding (ICS-MCB): a new tool for analysis of interphase chromosomes in their integrity. Biomol Eng 24: 415-417.
57. Iourov IY, Vorsanov SG, Liehr T, Kolotii AD, Soloviev IV, Vostrikov VM, Uranova NA, Yurov YB (2008) Association of genome instability and neurodegeneration in the cerebral cortex and hippocampus in Alzheimer's disease brain: Evidences for a new pathogenetic mechanism of the disease. Int J Psychophysiol 69: 288.
58. Janicki SM, Monteiro MJ (1999) Presenilin overexpression arrests cells in the G1 phase of the cell cycle: arrest potentiated by the Alzheimer's disease PS2 (N141I) Mutant. Am J Pathol 155: 135-144.
59. Jellinger KA, Bancher C (1998) Neuropathology of Alzheimer's disease: A critical update J Neural Transm Suppl 54: 77-95.
60. Jeong SJ, Kim HS, Chang KA, Geum DH, Park CH, Seo JH, Rah JC, Lee JH, Choi SH, Lee SG, Kim K, Suh YH (2000) Subcellular localization of presenilins during mouse preimplantation development. FASEB J 14: 2171-2176.
61. Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE (2008) ApoE promotes the proteolytic degradation of Abeta. Neuron 58: 681-693.
62. Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004) Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPw,Ind) mice. Proc Natl Acad Sci U S A 101: 13363-13367.
63. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci U S A 101: 343-347.
64. Johnsingh AA, Johnston JM, Merz G, Xu J, Kotula L, Jacobsen JS, Tezapsidis N (2000). Altered binding of mutated presenilin with cytoskeleton-interacting proteins. FEBS Lett 465 53-58.
65. Kuhn HG, Cooper-Kuhn CM, Boekhoorn K, Lucassen PJ (2007) Changes in neurogenesis in dementia and Alzheimer mouse models: are they functionally relevant? Eur Arch Psychiatry Clin Neurosci 257: 281-289.
66. Khurana V, Lu Y, Steinhilb ML, Oldham S, Shulman JM, Feany MB (2006) TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol 16: 230-241.
67. Kimura N, Nakamura SI, Honda T, Takashima A, Nakayama H, Ono F, Sakakibara I, Doi K, Kawamura S, Yoshikawa Y (2001) Age-related changes in the localization of presenilin-1 in cynomolgus monkey brain. Brain Res 922: 30-41.
68. Kingsbury MA, Friedman B, McConnell MJ, Rehen SK, Yang AH, Kaushal D, Chun J (2005) Aneuploid neurons are functionally active and integrated into brain circuitry. Proc Natl Acad Sci U S A 102: 6143-6147.
69. Khurana V, Lu Y, Steinhilb ML, Oldham S, Shulman JM, Feany MB (2006) TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol 16: 230-241.
70. Knobloch M, Konietzko U, Krebs DC, Nitsch RM (2007) Intracellular Abeta and cognitive deficits precede betaamyloid deposition in transgenic arcAbeta mice. Neurobiol Aging 28: 1297-1306.
71. Konishi Y, Bonni A (2003) The E2F-Cdc2 cell-cycle pathway specifically mediates activity deprivation-induced apoptosis of postmitotic neurons. J Neurosci 23: 1649-1658.
72. Konietzko U, Goodger ZV, Meyer M, Kohli BM, Bosset J, Lahiri DK, Nitsch RM (2008) Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories. Neurobiol Aging (Epub ahead of print): doi:10.1016/j.neurobiolaging.2008.03.001
73. Korczyn AD (2008) The amyloid cascade hypothesis. Alzheimers Dement 4: 176-178.
74. Kovaleva NV (2007) Parental mosaicism for trisomy 21: problems with its detection and an approach to determining its population rate. Genet Test 11: 341-344.
75. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP (2002) Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci 22: 1752-1762.
76. Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ, Emokpae R Jr, Gorospe M, Mattson MP (2004) Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41: 549-561.
77. Kuan CY, Schloemer AJ, Lu A, Burns KA, Weng WL, Williams MT, Strauss KI, Vorhees CV, Flavell RA, Davis RJ, Sharp FR, Rakic P (2004) Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. J Neurosci 24: 10763-10772.
78. Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, Sinforiani E, Olivari L, Barcikowska M, Styczynska M, Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D (2008) Conformationally altered p53: a novel Alzheimer's disease marker? Mol Psychiatry 13: 641-647.
79. Lao JL, Beyer K, Fernández-Novoa L, Miguel-Hidalgo JJ, Vecino B, Alvarez XA, Cacabelos R (1996) Cytogenetic signs of genomic instability in Alzheimer's disease. Neurobiol Aging 17: S62-63.
80. Larner AJ (2008) Mutation negative "early-onset familial Alzheimer disease": consider screening for tau gene mutations. Alzheimer Dis Assoc Disord 22: 194-195.
81. Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K, Lee WH, Bradley A (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359: 288-294.
82. Lee HG, Zhu X, Castellani RJ, Nunomura A, Perry G, Smith MA (2007) Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses. J Pharmacol Exp Ther 321: 823-829.
83. Lee H, Zhu X, Richardson S, Perry G, Smith M (2008) Failure in the control of cell cycle causes neurodegeneration. Alzheimers Dement 4 (Suppl. 1): T614-T615.
84. LeBlank A (1995) Increased production of 4KDa amyloid beta peptide in serum-deprived human primary neuron cultures: possible involvement of apoptosis. J Neurosci 15: 7837-7846.
85. Li B, Yamamori H, Tatebayashi Y, Shafit-Zagardo B, Tanimukai H, Chen S, Iqbal K, Grundke-Iqbal I (2008) Failure of neuronal maturation in Alzheimer disease dentate gyrus. J Neuropathol Exp Neurol 67: 78-84.
86. Li J, Xu M, Zhou H, Ma J, Potter H (1997) Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90: 917-927.
87. Li X, Alafuzoff I, Soininen H, Winblad B, Pei JJ (2005) Levels of mTOR and its downstream targets 4E-BP1, eEF2 and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J 272: 4211-4220.
88. Liu L, Li Y, Van Eldik LJ, Griffin WS, Barger SW (2005) S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors. J Neurochem 92: 546-553.
89. Love S, Barber R, Wilcock GK (1999) Increased polyADPribosylation of nuclear proteins in Alzheimer's disease. Brain 122: 247-253.
90. Lovell MA, Xie C, Markesbery WR (2000) Decreased base excision repair and increased helicase activity in Alzheimer's disease brain. Brain Res 855: 116-123.
91. Lucarelli P, Piciullo A, Palmarino M, Verdecchia M, Saccucci P, Arpino C, Curatolo P (2004) Association between presenilin 1 - 48c/t polymorphism and Down's syndrome. Neurosci Lett 367: 88-91.
92. Ma D, Zhou P, Harbour JW (2003) Distinct mechanisms for regulating the tumor suppressors and antiapoptotic functions of Rb. J Biol Chem 278: 19358-19366.
93. Matrone C, Ciotti MT, Mercanti D, Marolda R, Calissano P (2008) NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons. Proc Natl Acad Sci U S A 105: 13139-13144.
94. McDonald DR, Bamberger ME, Combs CK, Landreth GE (2008) Beta-amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes. J Neurosci 18: 4451-60.
95. McPhie DL, Coopersmith R, Hines-Peralta A, Chen Y, Ivins KJ, Manly SP, Kozlowski MR, Neve KA, Neve RL (2003) DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. J Neurosci 23: 6914-6927.
96. McShea A, Wahl AF, Smith MA (1999) Re-entry into the cell cycle: a mechanism for neurodegeneration in Alzheimer disease. Med Hypotheses 52: 525-527.
97. McShea A, Lee H, Petersen RB, Casadesus G, Vincent I, Linford NJ, Funk JO, Shapiro RA, Smith MA (2007) Neuronal cell cycle re-entry mediates Alzheimer disease-type changes. Biochim Biophys Acta 1772: 467-472.
98. Mehes K, Kosztolanyi G (2004) Clinical manifestation of genetic instability oerlap one another. Pathol Oncol Res 10: 12-16.
99. Mensah A, Mulligan C, Linehan J, Ruf S, O'Doherty A, Grygalewicz B, Shipley J, Groet J, Tybulewicz V, Fisher E, Brandner S, Nizetic D (2007) An additional human chromosome 21 causes suppression of neural fate of pluripotent mouse embryonic stem cells in a teratoma model. BMC Dev Biol 29: 131.
100. Migliore L, Botto N, Scarpato R, Petrozzi L, Cipriani G, Bonuccelli U (1999) Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients. Cytogenet Cell Genet 87: 41-46.
101. Migliore L, Testa A, Scarpato R, Pavese N, Petrozzi L, Bonuccelli U (1997) Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease. Hum Genet 101: 299-305.
102. Migliore L, Fontana I, Trippi F, Colognato R, Coppedè F, Tognoni G, Nucciarone B, Siciliano G (2005) Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients. Neurobiol Aging 26: 567-573.
103. Migliore L, Boni G, Bernardini R, Trippi F, Colognato R, Fontana I, Coppede F, Sbrana I (2006) Susceptibility to chromosome malsegregation in lymphocytes of women who had a Down syndrome child in a young age. Neurobiol Aging 27: 710-716.
104. Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14: 55-61.
105. Moehlmann T, Winkler E, Xia X, Edbauer D, Murrell J, Capell A, Kaether C, Zheng H, Ghetti B, Haass C, Steiner H (2002) Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci U S A 99: 8025-8030.
106. Moorhead PS, Heyman A (1983) Chromosome studies of patients with Alzheimer's disease. Am J Med Genet 14: 545-556.
107. Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt A (2007) Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease. J Neurosci 27: 6859-6867.
108. Mrak RE, Griffin WS (2004) Trisomy 21 and the brain. J Neuropathol Exp Neurol 63: 679-685.
109. Mrak RE, Griffin WS (2005) Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26: 349-354.
110. Mullaart E, Boerrigter ME, Ravid R, Swaab DF, Vijg J (1990) Increased levels of DNA breakes in cerebral cortex of Alzheimer's patients. Neurobiol Aging 11: 169-173.
111. Nagarsheth MH, Viehman A, Lippa SM, Lippa CF (2006) Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease. J Neurol Sci 244: 111-116.
112. Nagy Z, Esiri MM, Smith AD (1998) The cell division cycle and the pathophysiology of Alzheimer's disease Neurosci 87: 731-739.
113. Nagy Z (2000) Cell cycle regulatory failure in neurons: causes and consequences. Neurobiol Aging 21: 761-769.
114. Nagy Z, Combrinck M, Budge M, McShane R (2002) Cell cycle kinesis in lymphocytes in the diagnosis of Alzheimer's disease. Neurosci Lett 317: 81-84.
115. Nagy Z (2007) The dysregulation of the cell cycle and the diagnosis of Alzheimer's disease. Biochim Biophys Acta 1772: 402-408.
116. Nordenson I, Adolfsson R, Beckman G, Bucht G, Winblad B (1980) Chromosomal abnormality in dementia of Alzheimer type. Lancet 8166: 481-482.
117. Nouspikel T, Hanawalt PC (2003) When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease. Bioessays 25: 168-173.
118. Nussbaum RL, Ellis CE (2003) Alzheimer's disease and Parkinson's disease. N Engl J Med 348: 1356-1364.
119. O'Doherty A, Ruf S, Mulligan C, Hildreth V, Errington ML, Cooke S, Sesay A, Modino S, Vanes L, Hernandez D, Linehan JM, Sharpe PT, Brandner S, Bliss TV, Henderson DJ, Nizetic D, Tybulewicz VL, Fisher EM (2005) An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309: 2033-2037.
120. Ohyagi Y, Asahara H, Chui DH, Tsuruta Y, Sakae N, Miyoshi K, Yamada T, Kikuchi H, Taniwaki T, Murai H, Ikezoe K, Furuya H, Kawarabayashi T, Shoji M, Checler F, Iwaki T, Makifuchi T, Takeda K, Kira J, Tabira T (2005) Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer's disease. FASEB J 19: 255-257.
121. Okochi M, Fukumori A, Jiang J, Itoh N, Kimura R, Steiner H, Haass C, Tagami S, Takeda M (2006) Secretion of the Notch-1 Abeta-like peptide during Notch signaling. J Biol Chem 281: 7890-8.
122. Oyama F, Cairns NJ, Shimada H, Oyama R, Titani K, Ihara Y (1994) Down's syndrome: Up-regulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination. J Neurochem 62: 1062-1066.
123. Park DS, Obeidat A, Giovanni A, Greene LA (2000) Cell cycle regulators in neuronal death evoked by excitotoxic stress: implications for neurodegeneration and its treatment, Neurobiol Aging 21: 771-781.
124. Pastor P, Goate AM (2004) Molecular genetics of Alzheimer's disease. Curr. Psychiatry Rep. 6: 125-133.
125. Patterson D, Costa A (2005) Down syndrome and genetics - a case of linked histories. Nat Rev Genet 6: 137-147.
126. Percy ME, Markovic VD, McLachlan DR, Berg JM, Hummel JT, Laing ME, Dearie TG, Andrews DF (1991) Family with 22-derived marker chromosome and lateonset dementia of the Alzheimer type: I. Application of a new model for estimation of the risk of disease associated with the marker. Am J Med Genet 39: 307-313.
127. Petersen MB, Karadima G, Samaritaki M, Avramopoulos D, Vassilopoulos D, Mikkelsen M (2000) Association between presenilin-1 polymorphism and maternal meiosis II errors in Down syndrome. Am J Med Genet 93: 366-372.
128. Petronis A (1999) Alzheimer's disease and Down syndrome: from meiosis to dementia. Exper Neurol 58: 401-413.
129. Pigino G, Pelsman A, Mori H, Busciglio J (2001) Presenilin-1 mutations reduce cytoskeletal association, deregulate neurite growth, and potentiate neuronal dystrophy and tau phosphorylation. J Neurosci 21: 834-842.
130. H. Potter (1991) Review and hypothesis: Alzheimer disease and Down syndrome. Chromosome 21 nondisjunction may underlie both disorders. Am J Hum Genet 48: 1192-1200.
131. Potter H (2005) Cell cycle and chromosome segregation defects in Alzheimer's disease. In: Cell-cycle mechanisms and neuronal death (Copani A, Nicoletti F, eds), pp 55-78. Georgetown, TX: Landes.
132. Potter H (2008) Down's syndrome and Alzheimer's disease: two sides of the same coin. Future Neurol 3: 29-37.
133. Potter H, Granic A, Boeras D, Crespo N, Padmanabhan J (2008) Alzheimer's mutant presenilin-1 and amyloid precursor protein genes cause chromosome missegregation and aneuploidy through the action of Abeta peptide. Alzheimer's and Dementia 4, Suppl 1, T346.
134. Potter H, Wefes IM, Nilsson LNG (2001) The inflammation induced pathological chaperones ACT and apoe4 are necessary catalysts of Alzheimer amyloid formation. Neurobiol Aging 22: 923-930.
135. Prasher VP, Farrer MJ, Kessling AM, Fisher EM, West RJ, Barber PC, Butler AC (1998) Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann Neurol 43: 380-383.
136. Raina AK, Zhu X, Smith MA (2004) Alzheimer's disease and the cell cycle. Acta Neurobiol Exp (Wars) 64: 107-112.
137. Rashidian J, Iyirhiaro GO, Park DS (2007) Cell cycle machinery and stroke. Biochim Biophys Acta 1772: 484-493.
138. Rauk A (2008) Why is the amyloid beta peptide of Alzheimer's disease neurotoxic? Dalton Trans 14: 1273-1282.
139. Reddy PH, McWeeney S, Park PB, Manczak M, Gutala RV, Partovi D, Jung Y, Yau V, Searles R, Mori M, Quinn J (2004) Gene expression profiles of transcripts in amyloid precurson protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum Mol Genet 13: 1225-1240.
140. Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BS, Kingsbury MA, Cabral KM, McConnell MJ, Anliker B, Fontanoz M, Chun J (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25: 2176-2180.
141. Richards BW (1974) Investigation of 142 mosaic mongols and mosaic parents of mongols: cytogenetic analysis and maternal age of birth. J Ment Defic Res 18: 199-204.
142. Rideout HJ, Wang Q, Park DS, Stefanis L (2003) Cyclin-dependent kinase activity is required for apoptotic death but not inclusion formation in cortical neurons after proteasomal inhibition. J Neurosci 23: 1237-1245.
143. Ringman JM, Rao PN, Lu PH, Cederbaum S (2008) Mosaicism for trisomy 21 in a patient with young-onset dementia: a case report and brief literature review. Arch Neurol 65: 412-415.
144. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerrière A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D (2006) APP locus dupication causes autosomal dominant early-onset Alzheimer's disease with cerebral amyloid angiopathy. Nat Genet 38: 24-26.
145. Rowe IF, Ridler MAC, Gibberd FB (1989) Presenile dementia associated with mosaic trisomy 21 in a patient with a Down syndrome child. Lancet 8656: 229.
146. Sala SG, Muñoz U, Bartolomé F, Bermejo F, Martín-Requero A (2008) HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol-lowering effects. J Pharmacol Exp Ther 324: 352-359.
147. Salehi A, Faizi M, Belichenko PV, Mobley WC (2007) Using mouse models to explore genotype-phenotype relationship in Down syndrome. Ment Retard Dev Disabil Res Rev 13: 207-214.
148. Schupf N, Kapell D, Lee JH, Ottman R, Mayeux R (1994) Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome. The Lancet 344: 353-356.
149. Schupf N, Kapell D, Nightingale B, Lee JH, Mohlenhoff J, Bewley S, Ottman R, Mayeux R (2001) Specificity of the fivefold increase in AD in mothers of adults with Down syndrome. Neurology 57: 979-984.
150. Schindowski K, Belarbi K, Bretteville A, Ando K, Buée L (2008) Neurogenesis and cell cycle-reactivated neuronal death during pathogenic tau aggregation. Genes Brain Behav 7 (Suppl. 1): 92-100.
151. Słomnicki LP, Léniak W (2008) A putative role of the Amyloid Precursor Protein Intracellular Domain (AICD) in transcription Acta Neurobiol Exp (Wars) 68: 219-228.
152. Spremo-Potparevic, Zivkivic L, Djelic N, Bajic V (2004) Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle. Exp Gerontol 39: 849-854.
153. Spremo-Potparević B, Zivkoví L, Djelić N, Plećas-Solarović B, Smith MA, Bajiæ V (2008) Premature centromere division of the X chromosome in neurons in Alzheimer's disease. J Neurochem 106: 2218-223.
154. Staessen C, Maes AM, Kirsch-Volders M, Susanne C (1983) Is there a predisposition for meiotic non-disjunction that may be detected by mitotic hyperploidy? Clinical Genetics 24: 184-190.
155. Stanton LR, Coetzee RH (2004) Down's syndrome and dementia. Adv Psych Treatment 10: 50-58.
156. Staropoli JF, Abeliovich A (2005) The ubiquitin-proteasome pathway is necessary for maintenance of the postmitotic status of neurons. J Mol Neurosci 27: 175-183.
157. Strittmatter WJ, Roses D (1995) Apolipoprotein E and Alzheimer disease. Proc Natl Acad Sci U S A 92: 4725-4727.
158. Suizu A, Ryo G, Wulf J, Lim J, Lu KP (2006) Pin1 regulates Centrosome Duplication, and its overexpression induces centrosome amplification, chromosome instability, and oncogenesis. Mol Cell Biol 26: 1463-1479.
159. Suram A, Hegde ML, Rao KS (2007) A new evidence for DNA nicking property of amyloid beta-peptide (1-42): relevance to Alzheimer's disease. Arch Biochem Biophys 463: 245-252
160. Suzuki T, Oishi M, Marshak DR, Czernik AJ, Nairn AC, Greengard P (1994) Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein. EMBO J 13: 1114-1122.
161. Swerdlow RH, Khan SM (2004) A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Med Hypotheses 63: 8-20.
162. Tagami S, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M (2008) Processes of beta-amyloid and intracellular cytoplasmic domain generation by presenilin/gammasecretase. Neurodegener Dis 5: 160-162.
163. Taupin P (2008) Alzheimer's disease, aneuploidy and neurogenesis. Med Sci Monit 14: LE6-6.
164. Teller JK, Russo C, DeBusk LM, Angelini G, Zaccheo D, Dagna-Bricarelli F, Scartezzini P, Bertolini S, Mann DM, Tabaton M, Gambetti P (1996) Presence of soluble amyloid β-peptide precedes amyloid plaque formation in Down's syndrome. Nature Medicine 2: 93-95.
165. Tezapsidis N, Merz PA, Merz G, Hong H (2003) Microtubular interactions of presenilin direct kinesis of Abeta peptide and its precursor. FASEB J 17: 1322-1324.
166. Thakur A, Siedlak SL, James SL, Bonda DJ, Rao A, Webber KM, Camins A, Pallàs M, Casadesus G, Lee HG, Bowser R, Raina AK, Perry G, Smith MA, Zhu X (2008) Retinoblastoma protein phosphorylation at pultiple sites is associated with neurofibrillary pathology in Alzheimer disease. Int J Clin Exp Pathol 1: 134-146.
167. Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58: 1791-800.
168. Tighe A, Ray-Sinha A, Staples OD, Taylor SS (2007) GSK-3 inhibitors induce chromosome instability. BMC Cell Biol 8: 34.
169. Thomas P, Fenech M (2008) Chromosome 17 and 21 aneuploidy in buccal cells is increased with ageing and in Alzheimer's disease. Mutagenesis 23: 57-65.
170. Trześniewska K, Brzyska M, Elbaum D (2008) Neurodegenerative aspects of protein aggregation. Acta Neurobiol Exp (Wars) 64: 41-52.
171. Uberti D, Cenini G, Olivari L, Ferrari-Toninelli G, Porrello E, Cecchi C, Pensalfini A, Liguri G, Govoni S, Racchi M, Maurizio M (2007) Over-expression of amyloid precursor protein in HEK cells alters p53 conformational state and protects against doxorubicin. J Neurochem 103: 322-333.
172. Van Duijn CM, Clayton DG, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Mortimer JA (1994) Interaction between genetic and environmental risk factors for Alzheimer's disease: a reanalysis of case-control studies - EURODEM Risk Factor Research Group. Genet Epidemiol 11: 539-551.
173. Venoux M, Delmouly K, Milhavet O, Vidal-Eychenié S, Giorgi D, Rouquier S (2008) Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9). BMC Genomics 9: 406.
174. Vincent I, Jicha G, Rosado M, Dickson DW (1997) Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 17: 3588-3598.
175. Vorsanova SG, Yurov IY, Demidova IA, Voinova-Ulas VY, Kravets VS, Solov'ev IV, Gorbachevskaya NL, Yurov YB (2007) Variability in the heterochromatin regions of the chromosomes and chromosomal anomalies in children with autism: identification of genetic markers of autistic spectrum disorders. Neurosci Behav Physiol 37: 553-558.
176. Ward BE, Cook RH, Robinson A, Austin JH (1979) Increased aneuploidy in Alzheimer disease. Am J Med Genet 3: 137-144.
177. Webber KM, Raina AK, Marlatt MW, Zhu X, Prat MI, Morelli L, Casadesus G, Perry G, Smith MA (2005) The cell cycle in Alzheimer's disease: a unique target for neuropharmacology. Mech Aging Dev 126: 1019-1025.
178. Weihl CC, Miller RJ, Roos RP (1999) The role of betacatenin stability in mutant PS1-associated apoptosis. Neuroreport 10: 2527-2532.
179. Wen Y, Yang, S-H, Liu R, Perez EJ, Brun-Zinkernagel AM, Koulen P (2007) Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Biochim Biophys Acta 1772: 473-483.
180. Whalley LJ, Carothers AD, Collyer S, De Mey R, Frackiewicz A (1982) A study of familial factors in Alzheimer's disease. Brit J Psychiat 140: 249-256.
181. Wisniewski HM, Rabe A, Wisniewski KE (1988) Neuropathology and Dementia in People with Down's Syndrome. CSH Lab Press, New York.
182. Wojda U, Salinska E, Kuznicki J (2008) Calcium ions in neuronal degeneration. IUBMB Life 60: 575-590.
183. Wu J, Basha MR, Zawia NH (2008) The environment, epigenetics and amyloidogenesis. J Mol Neurosci 34: 1-7.
184. Xu H, Sweeney D, Greengard P, Gandy S (1996) Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system. Proc Natl Acad Sci U S A 93: 4081-4084.
185. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 21: 2661-2668.
186. Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J Neurosci 23: 2557-2563.
187. Yang Y. Varvel NH, Lamb BT, Herrup K (2006) Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. J Neurosci 26: 775-784.
188. Yang Y, Herrup K (2007) Cell division In the CNS: Protective response or lethal event in post-mitotic neurons? Biochim Biophys Acta 1772: 457-466.
189. Yurov YB, Iourov IY, Monakhov VV, Soloviev IV, Vostrikov VM, Vorsanova SG (2005) The variation of aneuploidy frequency in the developing and adult human brain revealed by an interphase FISH study. J Histochem Cytochem 53: 385-390.
190. Yurov YB, Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Kutsev SI, Pellestor F, Beresheva AK, Demidova IA, Kravets VS, Monakhov VV, Soloviev IV (2007) Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLoS ONE. 27: e558.
191. Yurov YB, Iourov IY, Vorsanova SG, Demidova IA, Kravetz VS, Beresheva AK, Kolotii AD, Monakchov VV, Uranova NA, Vostrikov VM, Soloviev IV, Liehr T (2008) The schizophrenia brain exhibits low-level aneuploidy involving chromosome 1. Schizophr Res 98: 139-147.
192. Zekanowski C, Religa D, Graff C, Filipek S, Kuźnicki J (2004) Genetic aspects of Alzheimer's disease. Acta Neurobiol Exp (Wars) 64: 19-31.
193. Zhang Z, Hartmann H, Do VM, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Sommer B, van de Wetering M, Clevers H, Saftig P, De Strooper B, He X, Yankner BA (1998) Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 395: 698-702.
194. Zhu X, Lee HG, Perry G, Smith MA (2007) Alzheimer's disease, the two-hit hypothesis: an update. Biochim Bioph Acta 1882: 494-502.
195. Zivkovic L, Spremo-Potparevic B, Djelic N, Bajic V (2006) Analysis of premature centromere division (PCD) of the chromosome 18 in peripheral blood lymphocytes in Alzheimer disease patients. Mech Aging Devel 127: 892-896.