Cannabinoid CB₂Receptors and Fatty Acid Amide Hydrolase Are Selectively Overexpressed in Neuritic Plaque-Associated Glia in Alzheimer's Disease Brains

TLDR

The endocannabinoid system remains poorly understood, with limited knowledge of its components’ distribution, concentration, and function in the human brain, especially during disease. The study examined the status of fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors in postmortem brains of Alzheimer’s disease patients. Immunohistochemical analysis with specific polyclonal antibodies was performed on hippocampal and entorhinal cortex sections. FAAH and CB2 were abundantly and selectively expressed in neuritic plaque‑associated astrocytes and microglia, CB1 expression was unchanged, and hydrolase activity was elevated in plaques and surrounding tissue, indicating potential modulatory roles in neuroinflammation and therapeutic targets.

Abstract

The endocannabinoid system is still poorly understood. Recently, the basic elements that constitute it, i.e., membrane receptors, endogenous ligands, and mechanisms for termination of the signaling process, have been partially characterized. There is a considerable lack of information, however, concerning the distribution, concentration, and function of those components in the human body, particularly during pathological events. We have studied the status of some of the components of the endocannabinoid system, fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with Alzheimer's disease. Using specific polyclonal antibodies, we have performed immunohistochemical analysis in hippocampus and entorhinal cortex sections from brains of Alzheimer's disease patients. Our results show that both fatty acid amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively expressed in neuritic plaque-associated astrocytes and microglia, respectively, whereas the expression of CB1 receptors remains unchanged. In addition, the hydrolase activity seems to be elevated in the plaques and surrounding areas. Thus, some elements of the endocannabinoid system may be postulated as possible modulators of the inflammatory response associated with this neurodegenerative process and as possible targets for new therapeutic approaches.