• Neurobiology of aging · Nov 2013

    Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer's disease leads to enhanced cognitive impairment despite of a reduction in amyloid deposition.

    • Christoph Stumm, Christof Hiebel, Regina Hanstein, Martin Purrio, Heike Nagel, Andrea Conrad, Beat Lutz, Christian Behl, and Angela B Clement.
    • Institute for Pathobiochemistry, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
    • Neurobiol. Aging. 2013 Nov 1;34(11):2574-84.

    AbstractAlzheimer's disease (AD) is characterized by amyloid-β deposition in amyloid plaques, neurofibrillary tangles, inflammation, neuronal loss, and cognitive deficits. Cannabinoids display neuromodulatory and neuroprotective effects and affect memory acquisition. Here, we studied the impact of cannabinoid receptor type 1 (CB1) deficiency on the development of AD pathology by breeding amyloid precursor protein (APP) Swedish mutant mice (APP23), an AD animal model, with CB1-deficient mice. In addition to the lower body weight of APP23/CB1(-/-) mice, most of these mice died at an age before typical AD-associated changes become apparent. The surviving mice showed a reduced amount of APP and its fragments suggesting a regulatory influence of CB1 on APP processing, which was confirmed by modulating CB1 expression in vitro. Reduced APP levels were accompanied by a reduced plaque load and less inflammation in APP23/CB1(-/-) mice. Nevertheless, compared to APP23 mice with an intact CB1, APP23/CB1(-/-) mice showed impaired learning and memory deficits. These data argue against a direct correlation of amyloid plaque load with cognitive abilities in this AD mouse model lacking CB1. Furthermore, the findings indicate that CB1 deficiency can worsen AD-related cognitive deficits and support a potential role of CB1 as a pharmacologic target.Copyright © 2013 Elsevier Inc. All rights reserved.

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