Cell cycle activation and aneuploid neurons in Alzheimer's disease

Molecular Neurobiology

Volumn 46, Issue 1, 2012, Pages 125-135

  Arendt, Thomas ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Apoptosis; Brain development; Cell death; Chromosome segregation; DNA replication; Neuronal vulnerability

Indexed keywords

AMYLOID BETA PROTEIN; TAU PROTEIN;

ALZHEIMER DISEASE; ANEUPLOIDY; APOPTOSIS; ARTICLE; BRAIN DEVELOPMENT; CARCINOGENESIS; CELL CYCLE REGULATION; CHROMOSOME ABERRATION; CHROMOSOME MOSAICISM; DIPLOIDY; DNA CONTENT; DNA REPLICATION; HUMAN; MITOSIS; NERVE CELL DIFFERENTIATION; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVOUS SYSTEM DEVELOPMENT; NEUROPATHOLOGY; NONHUMAN; ONTOGENY; PATHOGENESIS; PHYLOGENY;

EID: 84868108541     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-012-8262-0     Document Type: Article

References (184)

1. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239-259
2. Arendt T (2001) Alzheimer's disease as a disorder of mechanisms underlying structural brain self-organization. Neuroscience 102:723-765 (Pubitemid 32155873)
3. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11 (7):909-913
4. 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(4):991-1002 (Pubitemid 28114194)
5. Braak H, Braak E (1996) Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 92(2):197-201 (Pubitemid 26248463)
6. Arendt T, Holzer M, Stobe A, Gartner U, Luth HJ, Bruckner MK, Ueberham U (2000) Activated mitogenic signaling induces a process of dedifferentiation in Alzheimer's disease that eventually results in cell death. Ann N Y Acad Sci 920:249-255 (Pubitemid 32056577)
7. Arendt T (1993) Neuronal dedifferentiation and degeneration in Alzheimer's disease. Biol Chem Hoppe-Seyler 374:911-912
8. Heintz N (1993) Cell-death and the cell-cycle-A relationship between transformation and neurodegeneration. Trends Biochem Sci 18:157-159 (Pubitemid 23142567)
9. Arendt T, Holzer M, Gartner U (1998) Neuronal expression of cycline dependent kinase inhibitors of the INK4 family in Alzheimer's disease. J Neural Transm 105:949-960 (Pubitemid 28539839)
10. Arendt T, Rodel L, Gartner U, Holzer M (1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer's disease. Neuroreport 7:3047-3049 (Pubitemid 26426387)
11. Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J Neurosci 18:2801-2807 (Pubitemid 28163210)
12. Ding XL, Husseman J, Tomashevski A, Nochlin D, Jin LW, Vincent I (2000) The cell cycle Cdc25A tyrosine phosphatase is activated in degenerating postmitotic neurons in Alzheimer's disease. Am J Pathol 157:1983-1990
13. McShea A, Harris PL, Webster KR, Wahl AF, Smith MA (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am J Pathol 150:1933-1939 (Pubitemid 27233067)
14. Nagy Z, Esiri MM, Cato AM, Smith AD (1997) Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathol (Berl) 94:6-15 (Pubitemid 27289096)
15. Nagy Z, Esiri MM, Smith AD (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathol (Berl) 93:294-300 (Pubitemid 27104426)
16. Smith TW, Lippa CF (1995) Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. J Neuropathol Exp Neurol 54:297-303
17. 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 (Pubitemid 27200586)
18. 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. Progr Neurobiol 71:83-248 (Pubitemid 38004483)
19. Herrup K, Arendt T (2002) Re-expression of cell cycle proteins induces neuronal cell death during Alzheimer's disease. J Alzheimers Dis 4:243-247 (Pubitemid 36090055)
20. Herrup K, Yang Y (2007) Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci 8:368-378 (Pubitemid 46652467)
21. Arendt T, Brückner MK (2007) Linking cell-cycle dysfunction in Alzheimer's disease to a failure of synaptic plasticity. Biochim Biophys Acta 1772(4):413-421 (Pubitemid 46400388)
22. Schmetsdorf S, Gartner U, Arendt T (2005) Expression of cell cycle-related proteins in developing and adult mouse hippocampus. Int J Dev Neurosci 23:101-112 (Pubitemid 40261242)
23. Schmetsdorf S, Gärtner U, Arendt T (2007) Constitutive expression of functionally active cyclin-dependent kinases and their binding partners suggests noncanonical functions of cell cycle regulators in differentiated neurons. Cereb Cortex 17:1821-1829 (Pubitemid 47216499)
24. Frank CL, Li-H T (2009) Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity. Neuron 62(3):312-326
25. Pearson RC, EsiriMM, Hiorns RW,Wilcock GK, Powell TP (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. PNAS 82:4531-4534 (Pubitemid 15233154)
26. Esiri MM, Chance SA (2006) Vulnerability to Alzheimer's pathology in neocortex: the roles of plasticity and columnar organization. J Alzheimers Dis 9(3 Suppl):79-89 (Pubitemid 44253301)
27. Nagy Z, Esiri MM, Jobst KA, Morris JH, King EM, McDonald B, Litchfield S, Barnetson L (1996) Clustering of pathological features in Alzheimer's disease: clinical and neuroanatomical aspects. Dementia 7:121-127 (Pubitemid 26125791)
28. Kosik KS, Rogers J, Kowall NW (1987) Senile plaques are located between apical dendritic clusters. J Neuropathol Exp Neurol 46:1-11 (Pubitemid 17232250)
29. Buldyrev SV, Cruz L, Gomez-Isla T, Gomez-Tortosa E, Havlin S, Le R, Stanley HE, Urbanc B, Hyman BT (2000) Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias. PNAS 97:5039-5043 (Pubitemid 30313667)
30. Duyckaerts C, Hauw JJ, Piette F, Rainsard C, Poulain V, Berthaux P, Escourolle R (1985) Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length. Acta Neuropathol 66:72-74 (Pubitemid 15138012)
31. Terry RD, Peck A, DeTeresa R, Schechter R, Horoupian DS (1981) Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 10:184-192 (Pubitemid 11053105)
32. Chance SA, Casanova MF, Switala AE, Crow TJ, Esiri MM (2006) Minicolumn thinning in temporal lobe association cortex but not primary auditory cortex in normal human ageing. Acta Neuropathol 111:459-464
33. Colombo JA, Quinn B, Puissant V (2002) Disruption of astroglial interlaminar processes in Alzheimer's disease. Brain Res Bull 58:235-242 (Pubitemid 34753096)
34. Armstrong RA, Cairns NJ, Lantos PL (1997) Dementia with Lewy bodies: clustering of Lewy bodies in human patients. Neurosci Lett 224(1):41-44 (Pubitemid 27112865)
35. Armstrong RA, Cairns NJ, Lantos PL (1998) Clustering of Pick bodies in patients with Pick's disease. Neurosci Lett 242(2):81-84 (Pubitemid 28082998)
36. Casanova MF (2003) Modular concepts of brain organization and the neuropathology of psychiatric conditions. Psychiatr Res 118:101-102 (Pubitemid 36577563)
37. Rapoport SI (1988) Brain evolution and Alzheimer's disease. Rev Neurol (Paris) 144:79-90 (Pubitemid 18084143)
38. Kaushal D, Contos JJ, Treuner K, Yang AH, Kingsbury MA, Rehen SK, McConnell MJ, Okabe M, Barlow C, Chun J (2003) Alteration of gene expression by chromosome loss in the postnatal mouse brain. J Neurosci 23:5599-5606 (Pubitemid 36807837)
39. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J (2001) Chromosomal variation in neurons of the developing and adult mammalian nervous system. PNAS 98:13361-13366 (Pubitemid 33051368)
40. 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 2:e558
41. Martin O, Rubenstein JL (2001) A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2 (11):780-790 (Pubitemid 33674060)
42. Molyneaux BJ, Arlotta P, Menezes JR, Macklis JD (2007) Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci 8:427-437 (Pubitemid 46789231)
43. Kornack DR, Rakic P (1995) Radial and horizontal deployment of clonally related cells in the primate neocortex: relationship to distinct mitotic lineages. Neuron 15:311-321
44. Luskin MB, Parnavelas JG, Barfield JA (1993) Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells. J Neurosci 13:1730-1750 (Pubitemid 23095414)
45. Sidman RL, Rakic P (1973) Neuronal migration, with special reference to developing human brain: A review. Brain Res 62:1-35
46. Rakic P (1988) Specification of cerebral cortical areas. Science 241:170-176
47. Mountcastle VB (1957) Modality and topographic properties of single neurons of cat's somatic sensory cortex. J Neurophysiol 20:408-434
48. Mountcastle VB (1978) An organizing principle for cerebral function. In: Edelman GM, Mountcastle VB (eds) The mindful brain. MIT Press, Cambridge, pp 7-50
49. Mountcastle VB (1997) The columnar organization of the neocortex. Brain 120:701-722 (Pubitemid 27174104)
50. Kriegstein A, Noctor S, Martinez-Cerdeno V (2006) Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat Rev Neurosci 7:883-890 (Pubitemid 44624180)
51. Krubitzer L, Kahn DM (2003) Nature versus nurture revisited: an old idea with a new twist. Prog Neurobiol 70:33-52 (Pubitemid 36966640)
52. Kornack DR, Rakic P (1998) Changes in cell-cycle kinetics during the development and evolution of primate neocortex. PNAS 95:1242-1246 (Pubitemid 28124943)
53. Takahashi T, Nowakowski RS, Caviness VS Jr (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J Neurosci 15:6046-6057
54. Hill RS, Walsh CA (2005) Molecular insights into human brain evolution. Nature 437:64-67 (Pubitemid 41613427)
55. Cáceres M, Lachuer J, Zapala MA, Redmond JC, Kudo L, Geschwind DH, Lockhart DJ, Preuss TM, Barlow C (2003) Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci U S A 100(22):13030-13035 (Pubitemid 37340020)
56. Enard W, Khaitovich P, Klose J, Zöllner S, Heissig F, Giavalisco P, Nieselt-Struwe K, Muchmore E, Varki A, Ravid R, Doxiadis GM, Bontrop RE, Pääbo S (2002) Intra-and interspecific variation in primate gene expression patterns. Science 296(5566):340-343 (Pubitemid 34303687)
57. Gu J, Gu X (2003) Induced gene expression in human brain after the split from chimpanzee. Trends Genet 19(2):63-65 (Pubitemid 36120658)
58. Uddin M, Wildman DE, Liu G, Xu W, Johnson RM, Hof PR, Kapatos G, Grossman LI, Goodman M (2004) Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles. PNAS 101 (9):2957-2962 (Pubitemid 38327718)
59. Khaitovich P, Muetzel B, She X, Lachmann M, Hellmann I, Dietzsch J, Steigele S, Do HH, Weiss G, Enard W, Heissig F, Arendt T, Nieselt-Struwe K, Eichler EE, Pääbo S (2004) Regional patterns of gene expression in human and chimpanzee brains. Genome Res 14(8):1462-1473 (Pubitemid 39198896)
60. Khaitovich P, Weiss G, Lachmann M, Hellmann I, Enard W, Muetzel B, Wirkner U, Ansorge W, Pääbo S (2004) A neutral model of transcriptome evolution. PLoS Biol 2(5):E132
61. Thomson RY, Frazer SC (1954) The deoxyribonucleic acid content of individual rat cell nuclei. Exp Cell Res 6:367-383
62. Ueberham E, Lindner R, Kamprad M, Hiemann R, Hilger N, Woithe B, Mahn D, Cross M, Sack U, Gebhardt R, Arendt T, Ueberham U (2008) Oval cell proliferation in p16INK4a expressing mouse liver is triggered by chronic growth stimuli. J Cell Mol Med 12:622-638 (Pubitemid 351555140)
63. Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Yurov YB (2009) Increased chromosome instability dramatically disrupts neural genome integrity and mediates cerebellar degeneration in the ataxia-telangiectasia brain. Human Mol Gen 18:2656-2669
64. Iourov IY, Vorsanova SG, Liehr T, Yurov YB (2009) Aneuploidy in the normal, Alzheimer's disease and ataxia-telangiectasia brain: Differential expression and pathological meaning. Neurobiol Dis 34:212-220
65. 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. PNAS 102:6143-6147 (Pubitemid 40594269)
66. Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt T (2007) Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease. J Neurosci 27:6859-6867 (Pubitemid 47015903)
67. Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BSV, Kingsbury MA, Cabral KMS, McConnell MJ, Anliker B, Fontanoz M, Chun J (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25:2176-2180 (Pubitemid 40322258)
68. Vorsanova SG, Yurov YB, Iourov IY (2010) Human interphase chromosomes: A review of available molecular cytogenetic technologies. Mol Cytogen 3:1
69. Westra JW, Peterson SE, Yung YC, Mutoh T, Barral S, Chun J (2008) Aneuploid mosaicism in the developing and adult cerebellar cortex. J Comp Neurol 507:1944-1951 (Pubitemid 351468210)
70. Westra JW, Rivera RR, Bushman DM, Yung YC, Peterson SE, Barral S, Chun J (2010) Neuronal DNA content variation (DCV) with regional and individual differences in the human brain. J Comp Neurol 518:3981-4000
71. Brodsky VJ, Kusc AA (1962) Changes in the number of polyploid cells during postnatal development of rat tissue. Sci USSR 147:713-716
72. Müller H (1962) Cytophotometrische DNS-Messungen an Ganglienzellkernen des Nucleus dentatus beim Menschen. Naturwiss 49:243
73. Lapham LW (1965) The tetraploid DNA content of normal human Purkinje cells and its development during the perinatal period: A quantitative cytochemical study. Excerpta Med (Amst) Congr Ser 100:445-449
74. Lapham LW (1968) Tetraploid DNA content of Purkinje neurons of human cerebellar cortex. Science 159:310-312
75. Herman CJ, Lapham LW(1969) Neuronal polyploidy and nuclear volumes in the cat central nervous system. Brain Res 15:35-48
76. Mares V, Lodin Z, Sácha J (1973) A cytochemical and autoradiographic study of nuclear DNA in mouse Purkinje cells. Brain Res 53:273-289
77. Bernocchi G, Manfredi Romanini MG (1977) Chromatin cytochemistry as a tool for the functional interpretation of Purkinje's cells in rat cerebellum. Riv Istochim Norm Patol 21:131-142
78. Bernocchi G, Redi CA, Scherini E (1979) Feulgen-DNA content of the Purkinje neuron: "diploid" or "tetraploid"? Basic Appl Histochem 23:65-70 (Pubitemid 10124485)
79. Bernocchi G (1975) Contenuto in DNA e area nucleare dei neuroni durante l'istogenese cerebellare del ratto. Instituto Lombardo (Rend Sc) 109:143-161
80. Bregnard A, Knüsel A, Kuenzle CC (1975) Are all the neuronal nuclei polyploid? Histochemistry 43:59-61
81. Brodsky VJ, Sokolova GA, Manakova TE (1971) Multiple increase of DNA in the Purkinje cells of cerebellum in ontogenesis of rats. Ontogeny (USSR) 2:33-36
82. Brodsky VY, Agroskin LS, Lebedev EA, Marshak TL, Papayan GV, Segal OL, Sokolova GA, Yarygin KN (1974) Stability and variations of amount of DNA in a population of cerebellum cells. Z Obshchei Biol 35:917-925
83. Lentz RD, Lapham LW (1969) A quantitative cytochemical study of the DNA content of neurons of rat cerebellar cortex. J Neurochem 16:379-384
84. Lentz RD, Lapham LW (1970) Postnatal development of tetraploid DNA content in rat Purkinje cells: A quantitative cytochemical study. J Neuropathol Exp Neurol 29:43-56
85. Marshak TL, Maresh V, Brodskii V (1978) Number of Purkinje cells with an increased DNA content in rat cerebellum. Kolichestvo kletok Purkin'e s uvelichennym soderzhaniem DNK v mozzhechke krysy. Tsitolog 20:651-656
86. Marshak TL, Petruchuk EM, Aref'eva AM, Shalunova NV, Brodskiǐ VI (1976) O soderzhanii DNK V kletkakh Purkin'e mozzhechka krys, spontanno infitsirovannykh virusom Kilkhema. Biulleten' eksperimental'noǐ biologii i meditsiny 82:1274-1276
87. Sandritter W, Novokova V, Pilny J, Kiefer G (1967) Cytophotometrische Messungen des Nukleins ure-und Proteingehaltes von Ganglienzellen der Ratte während der postnatalen Entwicklung und im Alter. Zeitschr Zellforsch 80:145-152
88. Magkian I, Karalova EM (1975) [Basic factors in the polyploidization of cerebellar Purkinfe cells in chick embryogenesis. III. Kinetics of RNA and DNA in Purkinje cell nuclei]. Osenovnye faktory poliploidizatsii kletok Purkin'e mozzhechka v embriogeneze kur. III. Kinetika RNK i DNK v iadrakh kletok Purkin'e. Tsitolog 17:653-659
89. Herman CJ, Lapham LW (1968) DNA content of neurons in the cat hippocampus. Science 160:537
90. Bregnard A, Kuenzle CC, Ruch F (1977) Cytophotometric and autoradiographic evidence for post-natal DNA synthesis in neurons of the rat cerebral cortex. Exp Cell Res 107:151-157 (Pubitemid 8112725)
91. Nováková V, Sandritter W, Schlueter G (1970) DNA content of neurons in rat central nervous system. Exp Cell Res 60:454-456
92. Svanidze IK (1967) Cytophotometry of DNA amounts in nuclei of neurons and gliacytes of the cerebral cortex of rats at different ontogenetic stages. J Gen Biol (USSR) 28:697-708
93. Museridze DP, Svanidze IK (1972) Quantitative analysis of DNA in the neurons of the visual cortex of the brain at the early stages of postnatal ontogenesis of guinea pigs. Sov J Dev Biol 3:430-434
94. Kut AA, Iarygin VN (1965) Polipliodiia odnoiadernykh i dvuiadernykh neǐronov v verkhnem sheǐnom uzle krolika. Tsitolog 7:228-233
95. Swartz FJ, Bhatnagar KP (1981) Are CNS neurons polyploid? A critical analysis based upon cytophotometric study of the DNA content of cerebellar and olfactory bulbar neurons of the bat. Brain Res 208:267-281 (Pubitemid 11142855)
96. Bregnard A, Ruch F, Lutz H, Kuenzle CC (1979) Histones and DNA increase synchronously in neurons during early postnatal development of the rat forebrain cortex. Histochemistry 61:271-279 (Pubitemid 9243322)
97. Kuenzle CC, Bregnard A, Hübscher U, Ruch F (1978) Extra DNA in forebrain cortical neurons. Exp Cell Res 113:151-160 (Pubitemid 8336797)
98. Cohen J, Mares V, Lodin Z (1973) DNA content of purified preparations of mouse Purkinje neurons isolated by a velocity sedimentation technique. J Neurochem 20:651-657
99. Fujita S (1974) DNA constancy in neurons of the human cerebellum and spinal cord as revealed by Feulgen cytophotometry and cytofluorometry. J Comp Neurol 155:195-202
100. Fukuda M, Bohm N, Fujita S (1978) Cytophotometry and its biological application. Progr Histochem Cytochem 11:1-119
101. Mann DM, Yates PO, Barton CM (1978) The DNA content of Purkinje cells in mammals. J Comp Neurol 180:345-347 (Pubitemid 8345060)
102. Mann DM, Yates PO (1973) Polyploidy in the human nervous system: Part 1. The DNA content of neurones and glia of the cerebellum. J Neurol Sci 18:183-196
103. Morselt AF, Braakman DJ, James J (1972) Feulgen-DNA and fast-green histone estimations in individual cell nuclei of the cerebellum of young and old rats. Acta Histochem 43:281-286
104. Duijndam WA, Smeulders AW, van Duijn P, Verweij AC (1980) Optical errors in scanning stage absorbance cytophotometry. I. Procedures for correcting apparent integrated absorbance values for distributional, glare, and diffraction errors. J Histochem Cytochem 28:388-394 (Pubitemid 10155446)
105. Duijndam WA, van Duijn P, Riddersma SH (1980) Optical errors in scanning stage absorbance cytophotometry. II. Application of correction factors for residual distributional error, glare and diffraction error in practical cytophotometry. J Histochem Cytochem 28:395-400 (Pubitemid 10155447)
106. Fujita S, Fukuda M, Kitamura T, Satoru Y (1972) Two-wavelength-scanning method in Feulgen cytophotometry. Acta Histochem Cytochem 5:146-152
107. Brodsky VJ, Marshak TL, Mares V, Lodin Z, Fülöp Z, Lebedev EA (1979) Constancy and variability in the content of DNA in cerebellar Purkinje cell nuclei. A cytophotometric study. Histochemistry 59:233-248 (Pubitemid 9088419)
108. Mares V, van der Ploeg M (1980) Cytophotometric reinvestigation of DNA content in Purkinje cells of the rat cerebellum. Histochemistry 69:161-167 (Pubitemid 11168342)
109. Marshak TL, Mares V, Brodsky VY (1985) An attempt to influence DNA content in postmitotic Purkinje cells of the cerebellum. Acta Histochem 76:193-200 (Pubitemid 15061748)
110. Morillo SM, Escoll P, de La Hera A, Frade JM (2010) Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factor. PNAS 107:109-114
111. McConnell MJ, Kaushal D, Yang AH, Kingsbury MA, Rehen SK, Treuner K, Helton R, Annas EG, Chun J, Barlow C (2004) Failed clearance of aneuploid embryonic neural progenitor cells leads to excess aneuploidy in the Atm-deficient but not the Trp53-deficient adult cerebral cortex. J Neurosci 24:8090-8096 (Pubitemid 39280829)
112. 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 (Pubitemid 40344081)
113. Blaschke AJ, Staley K, Chun J (1996) Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development 122:1165-1174 (Pubitemid 26123891)
114. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 21:2661-2668 (Pubitemid 32298208)
115. Yurov YB, Vostrikov VM, Vorsanova SG, Monakhov VV, Iourov IY (2001) Multicolor fluorescent in situ hybridization on postmortem brain in schizophrenia as an approach for identification of low-level chromosomal aneuploidy in neuropsychiatric diseases. Brain Dev 23(Suppl 1):186-190
116. Gimelbrant A, Hutchinson JN, Thompson BR, Chess A (2007) Widespread monoallelic expression on human autosomes. Science 318:1136-1140 (Pubitemid 350134896)
117. Loerch PM, Lu T, Dakin KA, Vann JM, Isaacs A, Geula C, Wang J, Pan Y, Gabuzda DH, Li C, Prolla TA, Yankner BA (2008) Evolution of the aging brain transcriptome and synaptic regulation. PLoS One 3(10):e3329
118. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Månér S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M (2004) Large-scale copy number polymorphism in the human genome. Science 305:525-528 (Pubitemid 38971344)
119. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302:841 (Pubitemid 37339619)
120. Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2:280-291 (Pubitemid 33674776)
121. Rezaie R, Daly EM, Cutter WJ, Murphy DG, Robertson DM, Delisi LE, Mackay CE, Barrick TR, Crow TJ, Roberts N (2009) The influence of sex chromosome aneuploidy on brain asymmetry. Am J Med Genet B Neuropsychiatr Genet 150B(1):74-85
122. Bigner SH, Mark J, Bigner DD (1990) Cytogenetics of human brain tumors. Cancer Genet Cytogenet 47:141-154 (Pubitemid 20226620)
123. Yamada K, Kasama M, Kondo T, Shinoura N, Yoshioka M (1994) Chromosome studies in 70 brain tumors with special attention to sex chromosome loss and single autosomal trisomy. Cancer Genet Cytogenet 73:46-52 (Pubitemid 24205924)
124. Guttenbach M, Koschorz B, Bernthaler U, Grimm T, Schmid M (1995) Sex chromosome loss and aging: in situ hybridization studies on human interphase nuclei. Am J Hum Genet 57:1143-1150
125. Jacobs PA, Court BrownWM, Doll R (1961) Distribution of human chromosome counts in relation to age. Nature 191:1178-1180
126. Nowinski GP, Van Dyke DL, Tilley BC, Jacobsen G, Babu VR, Worsham MJ, Wilson GN, Weiss L (1990) The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history. Am J Hum Genet 46:1101-1111
127. Ly DH, Lockhart DJ, Lerner RA, Schultz PG (2000) Mitotic misregulation and human aging. Science 287:2486-2492 (Pubitemid 30185444)
128. Buckton KE, Whalley LJ, Lee M, Christie JE (1983) Chromosome changes in Alzheimer's presenile dementia. J Med Genet 20:46-51 (Pubitemid 13189476)
129. King RC, Stansfiled WD (1990) A dictionary of genetics, 4th edn. Oxford University Press, New York
130. Moorhead PS, Heyman A (1983) Chromosome studies of patients with Alzheimer's disease. Am J Med Genet 14:545-556 (Pubitemid 13108944)
131. Nordenson I, Adolfsson R, Beckman G, Bucht G, Winblad B (1980) Chromosomal abnormality in dementia of Alzheimer type. Lancet 1(8166):481-482
132. 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 (Pubitemid 351161354)
133. Gorman P, Roylance R (2006) Fluorescence in situ hybridization and comparative genomic hybridization. Meth Mol Med 120:269-295
134. Nordensson I, Beckman G, Adolfsson R, Bucht G, Winblad B (1983) Cytogenetic changes in patients with senile dementia. Age Ageing 12(4):285-295 (Pubitemid 15040701)
135. Smith A, Broe GA, Williamson M (1983) Chromosome aneuploidy in Alzheimer's disease. Clin Genet 24:54-57 (Pubitemid 13033517)
136. Ward BE, Cook RH, Robinson A, Austin JH (1979) Increased aneuploidy in Alzheimer disease. Am J Med Genet 3:137-144 (Pubitemid 10132347)
137. White BJ, Crandall C, Goudsmit J, Morrow CH, Alling DW, Gajdusek DC, Tijio JH (1981) Cytogenetic studies of familial and sporadic Alzheimer disease. Am J Med Genet 10:77-89 (Pubitemid 11003945)
138. Jacobs PA, Baikie AG, Court Brown WM, Strong JA (1959) The somatic chromosomes in mongolism. Lancet 1(7075):710
139. Lejeune J, Turpin R, Gautier M (1959) Mongolism: A chromosomal disease (trisomy). Bull Acad Natl Med 143:256-265
140. Lichter P, Cremer T, Tang CJ, Watkins PC, Manuelidis L, Ward DC (1988) Rapid detection of human chromosome 21 aberrations by in situ hybridization. PNAS 85:9664-9668 (Pubitemid 19027185)
141. Zheng YL, Ferguson-Smith MA,Warner JP, Ferguson-Smith ME, Sargent CA, Carter NP (1992) Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescence in situ hybridization using a cosmid contig. Prenat Diagn 12:931-943
142. DeLisi LE, Friedrich U, Wahlstrom J, Boccio-Smith A, Forsman A, Eklund K, Crow TJ (1994) Schizophrenia and sex chromosome anomalies. Schizophr Bull 20:495-505 (Pubitemid 24251259)
143. Kaplan AR (1970) Chromosomal mosaicisms and occasional acentric chromosomal fragments in schizophrenic patients. Biol Psychiatry 2:89-94
144. Kumra S,Wiggs E, Krasnewich D, Meck J, Smith AC, Bedwell J, Fernandez T, Jacobsen LK, Lenane M, Rapoport JL (1998) Brief report: association of sex chromosome anomalies with childhoodonset psychotic disorders. J Am Acad Child Adolesc Psych 37:292-296 (Pubitemid 28101227)
145. Kunugi H, Lee KB, Nanko S (1999) Cytogenetic findings in 250 schizophrenics: evidence confirming an excess of the X chromosome aneuploidies and pericentric inversion of chromosome 9. Schizophr Res 40:43-47 (Pubitemid 29459007)
146. Mors O, Mortensen PB, Ewald H (2001) No evidence of increased risk for schizophrenia or bipolar affective disorder in persons with aneuploidies of the sex chromosomes. Psychol Med 31:425-430 (Pubitemid 32294040)
147. Toyota T, Shimizu H, Yamada K, Yoshitsugu K, Meerabux J, Hattori E, Ichimiya T, Yoshikawa T (2001) Karyotype analysis of 161 unrelated schizophrenics: no increased rates of X chromosome mosaicism or inv(9), using ethnically matched and agestratified controls. Schizophr Res 52:171-179 (Pubitemid 33052508)
148. Callier P, Faivre L, Cusin V, Marle N, Thauvin-Robinet C, Sandre D, Rousseau T, Sagot P, Lacombe E, Faber V, Mugneret F (2005) Microcephaly is not mandatory for the diagnosis of mosaic variegated aneuploidy syndrome. Am J Med Genet A 137:204-207 (Pubitemid 41262689)
149. Jacquemont S, Bocéno M, Rival JM, Méchinaud F, David A (2002) High risk of malignancy in mosaic variegated aneuploidy syndrome. Am J Med Genet 109(1):17-21 (Pubitemid 34259949)
150. Kajii T, Ikeuchi T, Yang ZQ, Nakamura Y, Tsuji Y, Yokomori K, Kawamura M, Fukuda S, Horita S, Asamoto A (2001) Cancerprone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: report of five infants. Am J Med Genet 104:57-64
151. Kawame H, Sugio Y, Fuyama Y, Hayashi Y, Suzuki H, Kurosawa K, Maekawa K (1999) Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature. J Hum Genet 44:219-224 (Pubitemid 29313978)
152. Limwongse C, Schwartz S, Bocian M, Robin NH (1999) Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma. Am J Med Genet 82:20-24 (Pubitemid 29022293)
153. Thiel G, Losanowa T, Kintzel D, Nisch G, Martin H, Vorpahl K, Witkowski R (1992) Karyotypes in 90 human gliomas. Cancer Genet Cytogenet 58:109-120
154. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011-7021 (Pubitemid 39331011)
155. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396-401 (Pubitemid 39551674)
156. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821-5828 (Pubitemid 37187480)
157. Arendt T, Mosch B, Morawski M (2009) Neuronal aneuploidy in health and disease: A cytomic approach to understand the molecular individuality of neurons. Int J Mol Sci 10:1609-1627
158. Lenz D, Mosch B, Bocsi J, Arendt T, Tarnok A (2004) Assessment of DNA replication in central nervous system by laser scanning cytometry. In: Nicolau DV (ed) Imaging, manipulation, and analysis of biomolecules, cells, and tissues II. 27-28 January 2004, San Jose, California, USA. SPIE, Bellingham, pp 146-156
159. Mosch B, Mittag A, Lenz D, Arendt T, Tárnok A (2006) Laser scanning cytometry in human brain slices. Cytometry A 69 (3):135-138
160. Arendt T, Brückner MK, Mosch B, Lösche A (2010) Selective cell death of hyperploid neurons in Alzheimer's disease. Am J Pathol 177:15-20
161. Geller LA, Potter H (1999) Chromosome missegregation and trisomy 21 mosaicism in Alzheimer's disease. Neurbiol Dis 6:167-179 (Pubitemid 29297818)
162. Iourov IY, Vorsanova SG, Yurov YB (2006) Chromosomal variation in mammalian neuronal cells: known facts and attractive hypotheses. Int Rev Cytol 249:143-191
163. Iourov IY, Vorsanova SG, Yurov YB (2008) Chromosomal mosaicism goes global. Mol Cytogen 1:26
164. Potter H (1991) Review and hypothesis: Alzheimer disease and Down syndrome-chromosome 21 nondisjunction may underlie both disorders. Am J Med Genet 48:1192-1200 (Pubitemid 21903084)
165. 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 (Pubitemid 351215587)
166. Granic A, Padmanabhan J, Norden M, Potter H (2010) Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP. Mol Biol Cell 21:511-520
167. Iourov I, Vorsanova S, Yurov Y (2011) Genomic landscape of the Alzheimer's disease brain: chromosome instability-aneuploidy, but not tetraploidy-mediates neurodegeneration. Neurodegen Dis 8:35-37, discussion 38-40
168. Kuenzle CC (1985) Enzymology of DNA replication and repair in the brain. Brain Res 357:231-245 (Pubitemid 16160409)
169. 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 (Pubitemid 30067701)
170. Mazzarello P, Poloni M, Spadari S, Focher F (1992) DNA repair mechanisms in neurological diseases: facts and hypotheses. J Neurol Sci 112:4-14
171. Nouspikel T, Hanawalt PC (2003) When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease. Bioessays 25:168-173 (Pubitemid 36222388)
172. Yang AH, Kaushal D, Rehen SK, Kriedt K, Kingsbury MA, McConnell MJ, Chun J (2003) Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells. J Neurosci 23:10454-10462 (Pubitemid 37444622)
173. Potter H (2005) Cell cycle and chromosome segregation defects in Alzheimer's disease. In: Copani A, Nicoletti F (eds) Cell-cycle mechanisms and neuronal death. Landes, Georgetown, pp 55-78
174. Potter H (1991) Review and hypothesis: Alzheimer disease and Down syndrome-chromosome 21 nondisjunction may underlie both disorders. Am J Human Gen 48:1192-1200 (Pubitemid 21903084)
175. Cherry LM, Funk J, Lesser JM, Lesam M (1992) Gender differences and their interpretation of genetic instability in Alzheimer's disease. Mutat Res 275:57-76
176. Migliore L, Boni G, Bernardini R, Trippi F, Colognato R, Fontana I, Coppedè F, Sbrana I (2006) Susceptibility to chromosome malsegregation in lymphocytes of women who had a Down syndrome child in young age. Neurobiol Aging 27:710-716
177. Migliore L, Botto N, Scarpato R, Petrozzi L, Cipriani G, Bonuccelli U (1999) Preferential occurence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients. Cytogenet Cell Genet 87:41-46 (Pubitemid 30021031)
178. 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. Human Genet 101:299-305 (Pubitemid 28197524)
179. Percy ME, Markovic VD, Dalton AJ, McLachlan DRC, Berg JM, Rusk ACM, Somerville MJ, Chodakowski B, Andrews DF (1993) Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer's disease. Am J Med Genet 45:584-588 (Pubitemid 23066421)
180. 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. Lancet 344:353-356 (Pubitemid 24248205)
181. 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 (Pubitemid 27381630)
182. Arendt T (2008) Differentiation and de-differentiation-neuronal cell cycle regulation during development and age-related neurodegenerative disorders. In: Lajtha A, Perez-Polo JR, Rossner S (eds) Handbook of neurochemistry and molecular neurobiology. Development and aging changes in the nervous system, 3rd edn. Springer, New York, pp 157-213
183. Vincent I, Rosado M, Davies P (1996) Mitotic mechanisms in Alzheimer's disease? J Cell Biol 132:413-425 (Pubitemid 26053445)
184. Arendt T (2000) Alzheimer's disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain. Neurobiol Aging 21(6):783-796