 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 16, 1710-1719, Copyright © 1996 by Society for Neuroscience
DNA damage and apoptosis in Alzheimer's disease: colocalization with c- Jun immunoreactivity, relationship to brain area, and effect of postmortem delay
AJ Anderson, JH Su and CW Cotman
Institute for Brain Aging and Dementia, University of California, Irvine 92717-4550, USA.
Many neurons in Alzheimer's disease (AD) exhibit terminal deoxynucleotidyl
transferase (TdT) labeling for DNA strand breaks with a distribution
suggestive of apoptosis. We have shown previously that immunoreactivity for
c-Jun is elevated in AD and found in association with neuronal pathology.
In addition, cultured neurons undergoing beta- amyloid-mediated apoptosis
exhibit a selective and prolonged induction of c-Jun. Consequently, we
conducted double-labeling experiments to examine whether c-Jun is
associated with DNA strand breaks in AD tissue; we observed a strong
colocalization between these markers. As would be predicted based on the
distribution of AD pathology, we also found that TdT labeling was prominent
in the entorhinal cortex, but absent or at very low levels in cerebellum.
Furthermore, we confirmed that postmortem delay (PMD) does not affect TdT
labeling within the limits used for tissue used in this study. However, in
contrast to previous studies, we report an increase in TdT labeling with
more extended PMDs. Finally, gel electrophoresis of genomic DNA isolated
from AD and control cases failed to reveal evidence for either an apoptotic
or a necrotic mechanism of cell death in AD, possibly because of a low
number of cells actually undergoing cell death at any given time. Our
findings support the hypothesis that DNA damage labeled using TdT reflects
neuronal vulnerability and cell loss associated with AD pathology, and that
at least a portion of the cells labeled with this technique is undergoing
apoptosis. Furthermore, in agreement with in vitro findings, these results
suggest a relationship between the expression of c-Jun and neuronal risk
and/or cell death in AD.
This article has been cited by other articles:
|
|
|
|
 
K.-H. Sun, H.-g. Lee, M. A. Smith, and K. Shah
Direct and Indirect Roles of Cyclin-dependent Kinase 5 as an Upstream Regulator in the c-Jun NH2-Terminal Kinase Cascade: Relevance to Neurotoxic Insults in Alzheimer's Disease
Mol. Biol. Cell,
November 1, 2009;
20(21):
4611 - 4619.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-S. Yang, A. Kumar, P. Stavrides, J. Peterson, C. M. Peterhoff, M. Pawlik, E. Levy, A. M. Cataldo, and R. A. Nixon
Neuronal Apoptosis and Autophagy Cross Talk in Aging PS/APP Mice, a Model of Alzheimer's Disease
Am. J. Pathol.,
September 1, 2008;
173(3):
665 - 681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Medeiros, R. D. S. Prediger, G. F. Passos, P. Pandolfo, F. S. Duarte, J. L. Franco, A. L. Dafre, G. Di Giunta, C. P. Figueiredo, R. N. Takahashi, et al.
Connecting TNF-{alpha} Signaling Pathways to iNOS Expression in a Mouse Model of Alzheimer's Disease: Relevance for the Behavioral and Synaptic Deficits Induced by Amyloid {beta} Protein
J. Neurosci.,
May 16, 2007;
27(20):
5394 - 5404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Malm, H. Iivonen, G. Goldsteins, V. Keksa-Goldsteine, T. Ahtoniemi, K. Kanninen, A. Salminen, S. Auriola, T. Van Groen, H. Tanila, et al.
Pyrrolidine Dithiocarbamate Activates Akt and Improves Spatial Learning in APP/PS1 Mice without Affecting {beta}-Amyloid Burden
J. Neurosci.,
April 4, 2007;
27(14):
3712 - 3721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W. Smith, D. D. Norton, M. Gorospe, H. Jiang, S. Nemoto, N. J. Holbrook, T. Finkel, and J. W. Kusiak
Phosphorylation of p66Shc and forkhead proteins mediates A{beta} toxicity
J. Cell Biol.,
April 25, 2005;
169(2):
331 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Wang, D. M. Walsh, M. J. Rowan, D. J. Selkoe, and R. Anwyl
Block of Long-Term Potentiation by Naturally Secreted and Synthetic Amyloid {beta}-Peptide in Hippocampal Slices Is Mediated via Activation of the Kinases c-Jun N-Terminal Kinase, Cyclin-Dependent Kinase 5, and p38 Mitogen-Activated Protein Kinase as well as Metabotropic Glutamate Receptor Type 5
J. Neurosci.,
March 31, 2004;
24(13):
3370 - 3378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Li, L. Yang, K. Lindholm, Y. Konishi, X. Yue, H. Hampel, D. Zhang, and Y. Shen
Tumor Necrosis Factor Death Receptor Signaling Cascade Is Required for Amyloid-{beta} Protein-Induced Neuron Death
J. Neurosci.,
February 18, 2004;
24(7):
1760 - 1771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Minogue, A. W. Schmid, M. P. Fogarty, A. C. Moore, V. A. Campbell, C. E. Herron, and M. A. Lynch
Activation of the c-Jun N-terminal Kinase Signaling Cascade Mediates the Effect of Amyloid-{beta} on Long Term Potentiation and Cell Death in Hippocampus: A ROLE FOR INTERLEUKIN-1{beta}?
J. Biol. Chem.,
July 18, 2003;
278(30):
27971 - 27980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Qahwash, K. L. Weiland, Y. Lu, R. W. Sarver, R. F. Kletzien, and R. Yan
Identification of a Mutant Amyloid Peptide That Predominantly Forms Neurotoxic Protofibrillar Aggregates
J. Biol. Chem.,
June 13, 2003;
278(25):
23187 - 23195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Sponne, A. Fifre, B. Drouet, C. Klein, V. Koziel, M. Pincon-Raymond, J.-L. Olivier, J. Chambaz, and T. Pillot
Apoptotic Neuronal Cell Death Induced by the Non-fibrillar Amyloid-beta Peptide Proceeds through an Early Reactive Oxygen Species-dependent Cytoskeleton Perturbation
J. Biol. Chem.,
January 24, 2003;
278(5):
3437 - 3445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Wei, D. D. Norton, X. Wang, and J. W. Kusiak
A{beta} 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to neuronal apoptosis
Brain,
September 1, 2002;
125(9):
2036 - 2043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ribera, V. Ayala, and J. E. Esquerda
c-Jun-like Immunoreactivity in Apoptosis Is the Result of a Crossreaction with Neoantigenic Sites Exposed by Caspase-3-mediated Proteolysis
J. Histochem. Cytochem.,
July 1, 2002;
50(7):
961 - 972.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
W. Wei, X. Wang, and J. W. Kusiak
Signaling Events in Amyloid beta -Peptide-induced Neuronal Death and Insulin-like Growth Factor I Protection
J. Biol. Chem.,
May 10, 2002;
277(20):
17649 - 17656.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Savage, Y.-G. Lin, J. R. Ciallella, D. G. Flood, and R. W. Scott
Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition
J. Neurosci.,
May 1, 2002;
22(9):
3376 - 3385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Morishima, Y. Gotoh, J. Zieg, T. Barrett, H. Takano, R. Flavell, R. J. Davis, Y. Shirasaki, and M. E. Greenberg
{beta}-Amyloid Induces Neuronal Apoptosis Via a Mechanism that Involves the c-Jun N-Terminal Kinase Pathway and the Induction of Fas Ligand
J. Neurosci.,
October 1, 2001;
21(19):
7551 - 7560.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bothwell, G. E. Meredith, J. Phillips, H. Staunton, C. Doherty, E. Grigorenko, S. Glazier, S. A. Deadwyler, C. A. O'Donovan, and M. Farrell
Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy
J. Neurosci.,
July 1, 2001;
21(13):
4789 - 4800.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Lucassen, M. B. Muller, F. Holsboer, J. Bauer, A. Holtrop, J. Wouda, W. J. G. Hoogendijk, E. R. De Kloet, and D. F. Swaab
Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure
Am. J. Pathol.,
February 1, 2001;
158(2):
453 - 468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Park, E. J. Morris, R. Bremner, E. Keramaris, J. Padmanabhan, M. Rosenbaum, M. L. Shelanski, H. M. Geller, and L. A. Greene
Involvement of Retinoblastoma Family Members and E2F/DP Complexes in the Death of Neurons Evoked by DNA Damage
J. Neurosci.,
May 1, 2000;
20(9):
3104 - 3114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Q. Truong-Tran, L. H. Ho, F. Chai, and P. D. Zalewski
Cellular Zinc Fluxes and the Regulation of Apoptosis/Gene-Directed Cell Death
J. Nutr.,
May 1, 2000;
130(5):
1459S - 1466.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Stadelmann, T. L. Deckwerth, A. Srinivasan, C. Bancher, W. Bruck, K. Jellinger, and H. Lassmann
Activation of Caspase-3 in Single Neurons and Autophagic Granules of Granulovacuolar Degeneration in Alzheimer’s Disease : Evidence for Apoptotic Cell Death
Am. J. Pathol.,
November 1, 1999;
155(5):
1459 - 1466.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Imafuku, T. Masaki, M. Waragai, S. Takeuchi, M. Kawabata, S.-i. Hirai, S. Ohno, L.E. Nee, C.F. Lippa, I. Kanazawa, et al.
Presenilin 1 Suppresses the Function of C-Jun Homodimers via Interaction with Qm/Jif-1
J. Cell Biol.,
October 4, 1999;
147(1):
121 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. LeBlanc, H. Liu, C. Goodyer, C. Bergeron, and J. Hammond
Caspase-6 Role in Apoptosis of Human Neurons, Amyloidogenesis, and Alzheimer's Disease
J. Biol. Chem.,
August 13, 1999;
274(33):
23426 - 23436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Walter, A. Schindzielorz, J. Grunberg, and C. Haass
Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis
PNAS,
February 16, 1999;
96(4):
1391 - 1396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Ivins, J. K. Ivins, J. P. Sharp, and C. W. Cotman
Multiple Pathways of Apoptosis in PC12 Cells. CrmA INHIBITS APOPTOSIS INDUCED BY beta -AMYLOID
J. Biol. Chem.,
January 22, 1999;
274(4):
2107 - 2112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhou, S. A. Summers, M. J. Birnbaum, and R. N. Pittman
Inhibition of Akt Kinase by Cell-permeable Ceramide and Its Implications for Ceramide-induced Apoptosis
J. Biol. Chem.,
June 26, 1998;
273(26):
16568 - 16575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Guo, S. Christakos, N. Robinson, and M. P. Mattson
Calbindin D28k blocks the proapoptotic actions of mutant presenilin 1: Reduced oxidative stress and preserved mitochondrial function
PNAS,
March 17, 1998;
95(6):
3227 - 3232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Luo, H. Umegaki, X. Wang, R. Abe, and G. S. Roth
Dopamine Induces Apoptosis through an Oxidation-involved SAPK/JNK Activation Pathway
J. Biol. Chem.,
February 6, 1998;
273(6):
3756 - 3764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Vostrov and W. W. Quitschke
The Zinc Finger Protein CTCF Binds to the APBbeta Domain of the Amyloid beta -Protein Precursor Promoter. EVIDENCE FOR A ROLE IN TRANSCRIPTIONAL ACTIVATION
J. Biol. Chem.,
December 26, 1997;
272(52):
33353 - 33359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ninkina, M. Grashchuck, V. L. Buchman, and A. M. Davies
TrkB Variants with Deletions in the Leucine-rich Motifs of the Extracellular Domain
J. Biol. Chem.,
May 16, 1997;
272(20):
13019 - 13025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Pang and J. W. Geddes
Mechanisms of Cell Death Induced by the Mitochondrial Toxin 3-Nitropropionic Acid: Acute Excitotoxic Necrosis and Delayed Apoptosis
J. Neurosci.,
May 1, 1997;
17(9):
3064 - 3073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Paradis, H. Douillard, M. Koutroumanis, C. Goodyer, and A. LeBlanc
Amyloid beta Peptide of Alzheimer's Disease Downregulates Bcl-2 and Upregulates Bax Expression in Human Neurons
J. Neurosci.,
December 1, 1996;
16(23):
7533 - 7539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
