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bioRxiv · 10.1101/2022.07.26.501500

Evaluation of CB2R expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease

Kecheliev, V.·Spinelli, F.·Herde, A.·Haider, A.·Mu, L.·Klohs, J.·Ametamey, S.·Ni, R.
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Abstract

Neuroinflammation plays an important role in the pathophysiology of Alzheimers disease. The cannabinoid type 2 receptor (CB2R) is an emerging target for neuroinflammation and therapeutics of Alzheimers disease. Here, we aimed to assess the alterations in brain CB2R levels and evaluate novel CB2R imaging tracers in the arcA{beta} mouse model of Alzheimers disease amyloidosis. Immunohistochemical staining for A{beta} deposits (6E10), microgliosis (anti-Iba1 and anti-CD68 antibodies), astrocytes (GFAP) and the anti-CB2R antibody was performed on brain slices from arcA{beta} mice 17 months of age. Autoradiography using the CB2R imaging probes [18F]RoSMA-18-d6, [11C]RSR-056 and [11C]RS-028 and mRNA analysis were performed in brain tissue from arcA{beta} and nontransgenic littermate (NTL) mice at 6, 17, and 24 months of age. Specific increased CB2R immunofluorescence intensities on the increased number of GFAP-positive astrocytes and Iba1-positive microglia were detected in the hippocampus and cortex of 17-month-old arcA{beta} mice compared to NTL mice. CB2R immunofluorescence was higher in the glial cells inside 6E10-positive amyloid-{beta} deposits than peri-plaque with a low background. Ex vivo autoradiography showed that the binding of [18F]RoSMA-18-d6 and [11C]RSR-056 was comparable in arcA{beta} and NTL mice at 6, 17 and 24 months. The level of Cnr2 mRNA expression in the brain was not significantly different between arcA{beta} and NTL mice at 6, 17 or 24 months. In conclusion, we demonstrated pronounced specific increases in microglial and astroglial CB2R expression levels in a model of AD-related cerebral amyloidosis/AD mouse model, emphasizing CB2R as a suitable target for imaging neuroinflammation.

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Kecheliev, V., Spinelli, F., Herde, A., Haider, A., Mu, L., Klohs, J., Ametamey, S., Ni, R.. 2022-07-27. Evaluation of CB2R expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease. https://doi.org/10.1101/2022.07.26.501500

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