[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

► CB1 receptors (CB1Rs) have a neuromodulatory role in Alzheimer’s disease (AD).
► [125I]SD-7015 is a new CB1R selective radioligand for autoradiography (ARG) studies.
► ARG with [125I]SD-7015 in human AD brain shows CB1R density increases in early AD.
► Early CB1R density increases are followed by decreases during later disease stages.
► Our observations support the neuromodulatory role of the CB1Rs in AD.