 |
|
Neuronal Cyclooxygenase 2 Expression in the Hippocampal Formation as a Function of the Clinical Progression of Alzheimer Disease
Lap Ho, PhD;
Dushyant Purohit, MD;
Vahram Haroutunian, PhD;
James D. Luterman, PhD;
Fitzroy Willis, MS;
Jan Naslund, PhD;
Joseph D. Buxbaum, PhD;
Richard C. Mohs, PhD;
Paul S. Aisen, MD;
Giulio Maria Pasinetti, MD, PhD
Arch Neurol. 2001;58:487-492.
Background Prior studies have shown that cyclooxygenase 2 (COX-2), an enzyme involved
in inflammatory mechanisms and neuronal activities, is up-regulated in the
brain with Alzheimer disease (AD) and may represent a therapeutic target for
anti-inflammatory treatments.
Objective To explore COX-2 expression in the brain as a function of clinical progression
of early AD.
Design and Main Outcome Measures Using semiquantitative immunocytochemistry, we analyzed COX-2 protein
content in the hippocampal formation in 54 postmortem brain specimens from
patients with normal or impaired cognitive status.
Setting and Patients Postmortem study of nursing home residents.
Results The immunointensity of COX-2 signal in the CA3 and CA2 but not CA1 subdivisions
of the pyramidal layers of the hippocampal formation of the AD brain increased
as the disease progressed from questionable to mild clinical dementia as assessed
by Clinical Dementia Rating. COX-2 signal was increased in all 3 regions examined
among cases characterized by severe dementia.
Conclusion Neuronal COX-2 content in subsets of hippocampal pyramidal neurons may
be an indicator of progression of dementia in early AD.
From the Neuroinflammation Research Laboratories (Drs Ho, Luterman,
and Pasinetti and Mr Willis) and Departments of Pathology (Dr Purohit) and
Psychiatry (Drs Haroutunian, Buxbaum, and Mohs), The Mount Sinai School of
Medicine, New York, NY; Department of Clinical Neuroscience, Karolinska Institutet,
Huddinge, Sweden (Dr Naslund); and Department of Neurology, Georgetown University
Medical Center, Washington, DC (Dr Aisen).
Corresponding author and reprints: Giulio Maria Pasinetti, MD, PhD,
Neuroinflammation Research Laboratories, Department of Psychiatry, Box 1229,
Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029
(e-mail: gp2{at}doc.mssm.edu).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2001;58(3):523-525.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Prostaglandin E2 Stimulates the Production of Amyloid-{beta} Peptides through Internalization of the EP4 Receptor
Hoshino et al.
J. Biol. Chem. 2009;284:18493-18502.
ABSTRACT
| FULL TEXT
Cyclooxygenase-2 inhibition improves amyloid-{beta}-mediated suppression of memory and synaptic plasticity
Kotilinek et al.
Brain 2008;131:651-664.
ABSTRACT
| FULL TEXT
Involvement of Prostaglandin E2 in Production of Amyloid-beta Peptides Both in Vitro and in Vivo
Hoshino et al.
J. Biol. Chem. 2007;282:32676-32688.
ABSTRACT
| FULL TEXT
Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs
Townsend and Pratico
FASEB J. 2005;19:1592-1601.
ABSTRACT
| FULL TEXT
Type 2 Diabetes Is Negatively Associated With Alzheimer's Disease Neuropathology
Beeri et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2005;60:471-475.
ABSTRACT
| FULL TEXT
Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution
Calderon-Garciduenas et al.
Toxicol Pathol 2004;32:650-658.
ABSTRACT
Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition
Simmons et al.
Pharmacol. Rev. 2004;56:387-437.
ABSTRACT
| FULL TEXT
Peroxidase Activity of Cyclooxygenase-2 (COX-2) Cross-links {beta}-Amyloid (A{beta}) and Generates A{beta}-COX-2 Hetero-oligomers That Are Increased in Alzheimer's Disease
Nagano et al.
J. Biol. Chem. 2004;279:14673-14678.
ABSTRACT
| FULL TEXT
Cyclooxygenase (COX)-2 and COX-1 Potentiate {beta}-Amyloid Peptide Generation through Mechanisms That Involve {gamma}-Secretase Activity
Qin et al.
J. Biol. Chem. 2003;278:50970-50977.
ABSTRACT
| FULL TEXT
Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies
Etminan et al.
BMJ 2003;327:128.
ABSTRACT
| FULL TEXT
Effects of Rofecoxib or Naproxen vs Placebo on Alzheimer Disease Progression: A Randomized Controlled Trial
Aisen et al.
JAMA 2003;289:2819-2826.
ABSTRACT
| FULL TEXT
Role of Cyclooxygenase-2 in Neuronal Cell Cycle Activity and Glutamate-Mediated Excitotoxicity
Mirjany et al.
J. Pharmacol. Exp. Ther. 2002;301:494-500.
ABSTRACT
| FULL TEXT
Randomized pilot study of nimesulide treatment in Alzheimer's disease
Aisen et al.
Neurology 2002;58:1050-1054.
ABSTRACT
| FULL TEXT
|
