Intact cannabinoid CB1 receptors in the Alzheimer's disease cortex

The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer's disease (AD). However, the relation of CB1 receptors to cognitive function in AD is at present unclear. In this study, postmortem brain tissues from a cohort of prospectively assessed, neuropathologically confirmed AD patients and aged controls were used to measure CB1 receptors by immunoblotting, and a subset of subjects also had [3H]SR141716A binding. Correlational analyses were then performed for the neurochemical and cognitive data. We found that CB1 receptor levels in were unchanged AD in the brain regions assessed (frontal cortex, anterior cingulate gyrus, hippocampus, caudate nucleus). Within the AD group, frontal cortical CB1 immunoreactivity correlated with cognitive scores assessed within a year of death. Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function. Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD.

Research highlights▶ Cannabinoid CB1 receptors are preserved in various cortical regions of AD. ▶ CB1 receptor immunoreactivity correlates with pre-death cognitive scores in AD. ▶ Intact CB1 receptors may be associated with better cognitive function in AD. ▶ CB1 receptors should be further assessed as therapeutic targets in AD.