Reduced uptake of [11C]‐ABP688, a PET tracer for metabolic glutamate receptor 5 in hippocampus and amygdala in Alzheimer’s dementia

Treyer, Valérie; Gietl, Anton; Suliman, Husam; Gruber, Esmeralda; Meyer, Rafael; Buchmann, Andreas; Johayem, Anass; Unschuld, Paul G.; Nitsch, Roger M.; Buck, Alfred; Ametamey, Simon M.; Höck, Christoph

doi:10.1002/brb3.1632

Cited by 18 publications

(25 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Shimojo et al (2020) demonstrated a reduced level of inhibitory synapse by using [ 11 C]flumazenil at 2–3 month-of-age and a reduced level of excitatory synapse by using (E)-[ 11 C]ABP688 at 5–6 month-of-age in rTg4510 mice compared to wild-type littermates, preceding tau accumulation and brain regional atrophy ( Figures 2C,D ). Similarly, Treyer et al (2020) demonstrated a reduced (E)-[ 11 C]ABP688 uptake in the hippocampus and amygdala in patients with AD compared to healthy controls. Mecca et al (2020) showed an age-dependent reduction of [ 18 F]FPEB-PET level in health control cases probably due to tissue loss.…”

Section: Synaptic Neurotransmitter Receptorsmentioning

confidence: 82%

Positron Emission Tomography in Animal Models of Tauopathies

Cao

Kong

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.

show abstract

Section: Synaptic Neurotransmitter Receptorsmentioning

confidence: 82%

Positron Emission Tomography in Animal Models of Tauopathies

Cao

Kong

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…[ 11 C]Me-NB1 [124] for NMDAR GluN1/GluN2B subunits [125], as well as [ 18 F]FPEB, [ 11 C]ABP688 and [ 18 F]PSS232 for mGluR5 [126][127][128]. In patients with AD, PET using [ 18 F]FPEB [129] and [ 11 C]ABP688 [130] revealed consistant reductions in regional mGluR5 binding in the hippocampus and amygdala compared to non-demented controls. Sofar only mGluR5 imaging have been reported in amyloidosis animal models and showed conflicting results probably due to different animal models utilized (Table 2).…”

Section: Glutamate Receptorsmentioning

confidence: 99%

Positron Emission Tomography in Animal Models of Alzheimer’s Disease Amyloidosis

Ni¹

2021

Preprint

View full text Add to dashboard Cite

Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research, and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models are essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models as well as in patients with Alzheimer’s disease, These tools have facilitated our understanding of disease mechanisms, and provided longitudinal monitoring of treatment effect in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes, and discuss outstanding challenges in disease animal models and future outlook in on-chip characterization of imaging biomarkers towards clinical translation.

show abstract

“…The binding of [ 11 C]ABP688 ( 82 ) (DVR) was 27% lower in bilateral hippocampus of a group of ( n = 9) patients with Alzheimer’s disease, and by about 20% in amygdala of the same patients, relative to a significantly younger non-demented control group (69 vs. 77 years) [ 180 ]. In a [ 18 F]FPEB ( 86 ) PET study using a constant infusion design, the BP ND was reduced by 43% in hippocampus of ( n = 16) Alzheimer’s disease patients, compared to healthy age-matched and amyloid-negative controls [ 181 ].…”

Section: Glutamate Receptorsmentioning

confidence: 99%

A Review of Molecular Imaging of Glutamate Receptors

et al. 2020

View full text Add to dashboard Cite

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.

show abstract

Reduced uptake of [11C]‐ABP688, a PET tracer for metabolic glutamate receptor 5 in hippocampus and amygdala in Alzheimer’s dementia

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 56 publications

Positron Emission Tomography in Animal Models of Tauopathies

Positron Emission Tomography in Animal Models of Tauopathies

Positron Emission Tomography in Animal Models of Alzheimer’s Disease Amyloidosis

A Review of Molecular Imaging of Glutamate Receptors

Contact Info

Product

Resources

About