Vol. 6, No. 5-6, 2009
Issue release date: February 2010
Free Access
Neurodegenerative Dis 2009;6:221–229
Original Paper
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A Reevaluation of Tetraploidy in the Alzheimer’s Disease Brain

Westra J.W.a, b · Barral S.a · Chun J.a, b
aHelen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, Calif., and bBiomedical Sciences Graduate Program, School of Medicine, University of California, San Diego, Calif., USA
email Corresponding Author

 goto top of outline Key Words

  • Alzheimer’s disease
  • Cell cycle
  • Fluorescence in situ hybridization
  • Tetraploidy
  • Fluorescence-activated cell sorting
  • Neurons
  • Cerebral cortex
  • Hippocampus

 goto top of outline Abstract

Alzheimer’s disease (AD) is characterized by extensive neuronal death in distinct brain regions, including the frontal cortex and hippocampus, although the specific mechanisms of neuronal degeneration in AD remain a topic of intense scientific pursuit. One model for cell death in AD postulates that abortive cell cycle events in neurons, including tetraploidy, precede neuronal death, and novel therapeutics based on suppressing cell cycle re-entry are being pursued. Using DNA content fluorescence-activated cell sorting combined with fluorescence in situ hybridization and immunostaining, we analyzed neuronal nuclei from postmortem human brain samples from the frontal cortex and hippocampus of nondiseased and AD patients for evidence of tetraploidy. Here, we show that tetraploid nuclei are similarly prevalent in AD and control brains and are exclusively non-neuronal, contrasting with an absence of tetraploid neurons. Our findings demonstrate that neuronal tetraploidy is nonexistent in the AD brain and intimate a reevaluation of neuronal cell cycle re-entry as a therapeutic target for AD.

Copyright © 2009 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. Jerold Chun
The Scripps Research Institute, ICND 118
10550 North Torrey Pines Road
La Jolla, CA 92037 (USA)
Tel. +1 858 784 7039, Fax +1 858 784 7084, E-Mail jchun@scripps.edu

 goto top of outline Article Information

Received: September 8, 2008
Accepted after revision: March 16, 2009
Published online: September 9, 2009
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 0, Number of References : 37

 goto top of outline Publication Details

Neurodegenerative Diseases

Vol. 6, No. 5-6, Year 2009 (Cover Date: February 2010)

Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660-2854 (Print), eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD

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