Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease

Ahmad, Rawaha; Postnov, Andrey; Bormans, Guy; Versijpt, Jan; Vandenbulcke, Mathieu; Laere, Koen Van

doi:10.1007/s00259-016-3457-7

Cited by 76 publications

(66 citation statements)

References 42 publications

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“…Different from the expected findings, a recent 11 C-NE40 PET study has shown no in vivo CB 2 R upregulation in AD patients and no regional co-localization to Aβ deposits [70]. The authors thus argued for a possible lower affinity of the radioligand ( 11 C-NE40) to CB 2 R [70].…”

Section: Pet Molecular Imaging Of Neuroinflammationmentioning

confidence: 79%

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Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

Cerami

Iaccarino

Perani

2017

IJMS

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Neurodegeneration elicits neuroinflammatory responses to kill pathogens, clear debris and support tissue repair. Neuroinflammation is a dynamic biological response characterized by the recruitment of innate and adaptive immune system cells in the site of tissue damage. Resident microglia and infiltrating immune cells partake in the restoration of central nervous system homeostasis. Nevertheless, their activation may shift to chronic and aggressive responses, which jeopardize neuron survival and may contribute to the disease process itself. Positron Emission Tomography (PET) molecular imaging represents a unique tool contributing to in vivo investigating of neuroinflammatory processes in patients. In the present review, we first provide an overview on the molecular basis of neuroinflammation in neurodegenerative diseases with emphasis on microglia activation, astrocytosis and the molecular targets for PET imaging. Then, we review the state-of-the-art of in vivo PET imaging for neuroinflammation in dementia conditions associated with different proteinopathies, such as Alzheimer’s disease, frontotemporal lobar degeneration and Parkinsonian spectrum.

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Section: Pet Molecular Imaging Of Neuroinflammationmentioning

confidence: 79%

“…The authors thus argued for a possible lower affinity of the radioligand ( 11 C-NE40) to CB 2 R [70]. A pilot PET study with 11 C-radiolabeled AA showed in few AD patients a widely elevated tracer uptake in different neocortical regions [71].…”

Section: Pet Molecular Imaging Of Neuroinflammationmentioning

confidence: 99%

Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

Cerami

Iaccarino

Perani

2017

IJMS

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“…Further confirmation of the in vivo binding of [ 11 C]NE40 to CB2 was demonstrated in a rat which was sterotactically injected into the right striatum with an adeno‐associated viral vector encoding human CB2 with a point mutation . Based on these encouraging preclinical results and the fact that [ 11 C]NE40 is selective over other 51 different targets and has no toxicological effects in Wistar rats, clinical studies were performed in 6 healthy Caucasian male volunteers and AD patients . Whole‐body PET imaging in the healthy volunteers showed (1) high uptake in liver and intestine, suggesting the hepatobiliary pathway elimination; (2) stable standardized uptake value in the spleen over time due to the specific binding to the CB2 receptors constitutively expressed in this organ; and (3) slight brain uptake and moderately fast washout, in accordance with the low expression of CB2 in healthy brain .…”

Section: Cb2 Radioligands For Pet Imagingmentioning

confidence: 89%

“…Structures of compounds A , [ 11 C]A‐836339 (Yao et al, Horti et al, Savonenko et al, and Pottier et al) and [ 18 F]1 (Moldovan et al); B , [ 11 C]NE40 (Evens et al, Ahmad et al, and Vandeputte et al) and [ 11 C]KP23 (Mu et al); C , [ 11 C]KD2 (Mu et al), [ 11 C]RS‐016 (Slavik et al and Meletta et al), and [ 18 F]RS‐126 (Slavik et al); D , RSR‐056 (Slavik et al); E , [ 18 F]‐ d 2 ‐2 (Hortala et al); F , [ 18 F]3 (Yrjölä et al)…”

Section: Cb2 Radioligands For Pet Imagingmentioning

confidence: 99%

Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor

Spinelli

Ametamey

2017

Labelled Comp Radiopharmac

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The cannabinoid type 2 (CB2) receptor is an immunomodulatory receptor mainly expressed in peripheral cells and organs of the immune system. The expression level of CB2 in the central nervous system under physiological conditions is negligible, however under neuroinflammatory conditions an upregulation of CB2 protein or mRNA mainly colocalized with activated microglial cells has been reported. Consequently, CB2 agonists have been confirmed to play a role in neuroprotective and anti-inflammatory processes. A suitable positron emission tomography radioligand for imaging CB2 would provide an invaluable research tool to explore the role of CB2 receptor expression in inflammatory disorders. In this review, we provide a summary of so far published CB2 radioligands as well as their in vitro and in vivo binding characteristics.

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“…CB2, an alternative membrane marker of activated microglial cells, is currently regarded as a critical protein which triggers multiple brain pathophysiological events involved in synaptic plasticity and neuroprotection (Chiurchiù et al, 2015). Several lines of evidence have offered new perspectives on the possible involvement of CB2 signaling in brain and spinal cord traumatic injury, as well as in several neurodegenerative disorders, including AD (Ahmad et al, 2016;Bisogno et al, 2016). These studies support the possibility that CB2 is part of a protective mechanism that is both acutely and chronically activated during neuropathology.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

Tang

Bao

et al. 2017

Genet. Mol. Res.

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ABSTRACT. Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR- 139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.

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Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease

Cited by 76 publications

References 42 publications

Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

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