[¹²⁵I]SD-7015 reveals fine modalities of CB₁ cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease.
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.
Department of Neurology, University of Debrecen, H-4012 Debrecen, Hungary.
Szabolcs
S
Farkas
Katalin
K
Nagy
Miklós
M
Palkovits
Gábor G
GG
Kovács
Zhisheng
Z
Jia
Sean
S
Donohue
Vic
V
Pike
Christer
C
Halldin
Domokos
D
Máthé
Tibor
T
Harkany
Balázs
B
Gulyás
László
L
Csiba
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001345:Autoradiography; D002138:Calibration; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011720:Pyrazoles; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects*; D014015:Tissue Banks
C572934:4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1