[¹²⁵I]SD-7015 reveals fine modalities of CB₁ cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease.

Abstract

The cannabinoid type-1 receptor (CB₁R) is one of the most abundant members of the G protein-coupled receptor family in the central nervous system. Once activated by their cognate ligands, endocannabinoids, CB₁Rs generally limit the timing of neurotransmitter release at many cortical synapses. Prior studies have indicated the involvement of CB₁R in neurodegeneration and in various neuronal insults, with an emphasis on their neuroprotective role. In the present study we used a novel selective CB₁R radioligand to investigate regional variations in CB₁R ligand binding as a factor of progressive Braak tau pathology in the frontal cortex of Alzheimer's disease (AD) patients. The frontal cortex was chosen for this study due to the high density of CB₁Rs and their well-characterized involvement in the progression of AD. Post-mortem prefrontal cortex samples from AD patients from Braak stages I to VI and controls were subjected to CB₁R autoradiography with [¹²⁵I]SD-7015 as radioligand. Regional concentration of [¹²⁵I]SD-7015, corresponding to, and thereby representing, regional CB₁R densities, were expressed in fM/g_tissue. The results show that CB₁R density inversely correlates with Braak tau pathology with the following tendency: controls <AD Braak stage V-VI <AD Braak stage III-IV <AD Braak stage I-II. Differences were significant between control and AD Braak stage I-II groups, as well as between controls and the AD group comprising all Braak stages. These findings indicate an up-regulation of the tissue binding of the selective CB₁R radioligand [¹²⁵I]SD7015 in human brains, allowing the detection of fine modalities of receptor expression and radioligand binding during the progression of AD.

• Authors: Szabolcs Farkas, Katalin Nagy, Miklós Palkovits, Gábor G Kovács, Zhisheng Jia, Sean Donohue, Vic Pike, Christer Halldin, Domokos Máthé, Tibor Harkany, Balázs Gulyás, László Csiba
• Journal: Neurochemistry international (Neurochem Int) Vol. 60 Issue 3 Pg. 286-91 (Feb 2012) ISSN: 1872-9754 [Electronic] England
• PMID: 22222721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
• Pyrazoles
• Radiopharmaceuticals
• Receptor, Cannabinoid, CB1

Topics

• Aged
• Aged, 80 and over
• Aging (physiology)
• Alzheimer Disease (diagnostic imaging, metabolism)
• Autoradiography
• Calibration
• Disease Progression
• Female
• Humans
• Male
• Middle Aged
• Prefrontal Cortex (diagnostic imaging, metabolism)
• Pyrazoles
• Radionuclide Imaging
• Radiopharmaceuticals
• Receptor, Cannabinoid, CB1 (drug effects)
• Tissue Banks