The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
In Vivo Detection of Age- and Disease-Related Increases in Neuroinflammation by18F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice
Open accessAbstract
Alzheimer's disease (AD) is the most common cause of dementia. Neuroinflammation appears to play an important role in AD pathogenesis. Ligands of the 18 kDa translocator protein (TSPO), a marker for activated microglia, have been used as positron emission tomography (PET) tracers to reflect neuroinflammation in humans and mouse models. Here, we used the novel TSPO-targeted PET tracer 18 F-GE180 (flutriciclamide) to investigate differences in neuroinflammation between young and old WT and APP/PS1dE9 transgenic (Tg) mice.In vivo PET scans revealed an overt age-dependent elevation in whole-brain uptake of 18 F-GE180 in both WT and Tg mice, and a significant increase in whole-brain uptake of 18 F-GE180 (peak-uptake and retention) in old Tg mice compared with young Tg mice and all WT mice. Similarly, the 18 F-GE180 binding potential in hippocampus was highest to lowest in old Tg > old WT > young Tg > young WT mice using MRI coregistration.Ex vivo PET and autoradiography analysis further confirmed our in vivo PET results: enhanced uptake and specific binding (SUV 75%) of 18 F-GE180 in hippocampus and cortex was highest in old Tg mice followed by old WT, young Tg, and finally young WT mice.18 F-GE180 specificity was confirmed by an in vivo cold tracer competition study. We also examined 18 F-GE180 metabolites in 4-month-old WT mice and found that, although total radioactivity declined over 2 h, of the remaining radioactivity, ∼90% was due to parent 18 F-GE180. In conclusion,18 F-GE180 PET scans may be useful for longitudinal monitoring of neuroinflammation during AD progression and treatment. SIGNIFICANCE STATEMENT Microglial activation, a player in Alzheimer's disease (AD) pathogenesis, is thought to reflect neuroinflammation. Using in vivo microPET imaging with a novel TSPO radioligand,18 F-GE180, we detected significantly enhanced neuroinflammation during normal aging in WT mice and in response to AD-associated pathology in APP/PS1dE9 Tg mice, an AD mouse model. Increased uptake and specific binding of 18 F-GE180 in whole brain and hippocampus were confirmed by ex vivo PET and autoradiography. The binding specificity and stability of 18 F-GE180 was further confirmed by a cold tracer competition study and a metabolite study, respectively. Therefore,18 F-GE180 PET imaging may be useful for longitudinal monitoring of neuroinflammation during AD progression and treatment and may also be useful for other neurodegenerative diseases.
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“Similarly, others have found that TSPO positive microglia, astrocytes and endothelium are all increased in models of Alzheimer’s-like neurodegeneration [48–51] and in postmortem human Alzheimer’s disease brains [27].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [49]
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Cites
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“Initially, neuroinflammatory responses may be a self-defense mechanism to protect the brain during disease and injury (Meda et al., 2001; Morgan et al., 2005; Tuppo and Arias, 2005; Hickman et al., 2008; Winkeler et al., 2010).”
BackgroundActivation of microglial cells by β-amyloid protein and interferon-γ
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Inflammation in Neurodegenerative Disease—A Double-Edged Sword
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Metadata
- Authors
- Liu, B., Le, K. X., Park, M.-A., Wang, S., Belanger, A. P., Dubey, S., Frost, J. L., Holton, P., Reiser, V., Jones, P. A., Trigg, W., Di Carli, M. F., & Lemere, C. A.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-11-25
- Volume
- 35
- Issue
- 47
- Pages
- 15716-15730
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6705465
- OpenAlex
- W2253390436
- Cited by
- 114
- References
- 73
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 11 · 2018: 14 · 2017: 17 · 2016: 9
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG040092)
- National Institute of Neurological Disorders and Stroke (R01NS136122)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, neuroinflammation, microglial activation, aging, hippocampus, microPET imaging, binding potential, tracer metabolism, Alzheimer's disease biomarkers
- MeSH terms
- Aging, Alzheimer Disease, Animals, Carbazoles, Fluorine Radioisotopes, Humans, Inflammation, Male, Mice, Inbred C57BL, Mice, Transgenic, Receptors, GABA, Disease Progression, Positron-Emission Tomography, Mice
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