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The Journal of Neuroscience, December 3, 2003, 23(35):11136-11141

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Cellular/Molecular
Cannabinoid CB₂ Receptors and Fatty Acid Amide Hydrolase Are Selectively Overexpressed in Neuritic Plaque-Associated Glia in Alzheimer's Disease Brains

Cristina Benito,^1 * Estefanía Núñez,^1 * Rosa M. Tolón,¹ Erica J. Carrier,² Alberto Rábano,¹ Cecilia J. Hillard,² and Julián Romero¹

¹Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, 28922 Alcorcón, Madrid, Spain, and ²Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

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.

Key words: Alzheimer; astrocyte; astroglia; cannabinoids; immunoreactivity; microglia; neuropathology

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Received July 18, 2003; revised September 15, 2003; accepted September 16, 2003.

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