PMID- 17596434
OWN - NLM
STAT- MEDLINE
DCOM- 20070801
LR  - 20220316
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 26
DP  - 2007 Jun 27
TI  - Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease.
PG  - 6859-67
AB  - Reactivation of the cell cycle, including DNA replication, might play a major 
      role in Alzheimer's disease (AD). A more than diploid DNA content in 
      differentiated neurons might alternatively result from chromosome mis-segregation 
      during mitosis in neuronal progenitor cells. It was our objective to distinguish 
      between these two mechanisms for aneuploidy and to provide evidence for a 
      functional cell cycle in AD. Using slide-based cytometry, chromogenic in situ 
      hybridization, and PCR amplification of alu-repeats, we quantified the DNA amount 
      of identified cortical neurons in normal human brain and AD and analyzed the link 
      between a tetraploid DNA content and expression of the early mitotic marker 
      cyclin B1. In the normal brain, the number of neurons with a more than diploid 
      content amounts to approximately 10%. Less than 1% of neurons contains a 
      tetraploid DNA content. These neurons do not express cyclin B1, most likely 
      representing constitutional tetraploidy. This population of cyclin B1-negative 
      tetraploid neurons, at a reduced number, is also present in AD. In addition, a 
      population of cyclin B1-positive tetraploid neurons of approximately 2% of all 
      neurons was observed in AD. Our results indicate that at least two different 
      mechanisms need to be distinguished giving rise to a tetraploid DNA content in 
      the adult brain. Constitutional aneuploidy in differentiated neurons might be 
      more frequent than previously thought. It is, however, not elevated in AD. In 
      addition, in AD some neurons have re-entered the cell cycle and entirely passed 
      through a functional interphase with a complete DNA replication.
FAU - Mosch, Birgit
AU  - Mosch B
AD  - Paul Flechsig Institute of Brain Research, Department of Neuroanatomy, University 
      of Leipzig, D-04109 Leipzig, Germany.
FAU - Morawski, Markus
AU  - Morawski M
FAU - Mittag, Anja
AU  - Mittag A
FAU - Lenz, Dominik
AU  - Lenz D
FAU - Tarnok, Attila
AU  - Tarnok A
FAU - Arendt, Thomas
AU  - Arendt T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*genetics/physiopathology
MH  - *Aneuploidy
MH  - Brain/*metabolism/physiopathology
MH  - Brain Chemistry/*genetics
MH  - Cell Cycle/genetics
MH  - Cerebral Cortex/metabolism/physiopathology
MH  - Cyclin B/genetics
MH  - Cyclin B1
MH  - DNA Replication/*genetics
MH  - Genetic Markers/genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Humans
MH  - Mitosis/genetics
MH  - Neurons/metabolism/pathology
PMC - PMC6672221
EDAT- 2007/06/29 09:00
MHDA- 2007/08/02 09:00
PMCR- 2007/12/27
CRDT- 2007/06/29 09:00
PHST- 2007/06/29 09:00 [pubmed]
PHST- 2007/08/02 09:00 [medline]
PHST- 2007/06/29 09:00 [entrez]
PHST- 2007/12/27 00:00 [pmc-release]
AID - 27/26/6859 [pii]
AID - 3237953 [pii]
AID - 10.1523/JNEUROSCI.0379-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Jun 27;27(26):6859-67. doi: 10.1523/JNEUROSCI.0379-07.2007.