Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging
Open accessAbstract
Recent findings have led to a renewed interest and support for an active role of inflammation in neurodegenerative dementias and related neurologic disorders. Detection of neuroinflammation in vivo throughout the course of neurodegenerative diseases is of great clinical interest. Studies have shown that microglia activation (an indicator of neuroinflammation) may present at early stages of frontotemporal dementia (FTD), but the role of neuroinflammation in the pathogenesis of FTD is largely unknown. The first-generation translocator protein (TSPO) ligand ([(11)C]-PK11195) has been used to detect microglia activation in FTD, and the second-generation TSPO ligands have imaged neuroinflammation in vivo with improved pharmacokinetic properties. This paper reviews related literature and technical issues on mapping neuroinflammation in FTD with positron-emission tomography (PET) imaging. Early detection of neuroinflammation in FTD may identify new tools for diagnosis, novel treatment targets, and means to monitor therapeutic efficacy. More studies are needed to image and track neuroinflammation in FTD. It is anticipated that the advances of TSPO PET imaging will overcome technical difficulties, and molecular imaging of neuroinflammation will aid in the characterization of neuroinflammation in FTD. Such knowledge has the potential to shed light on the poorly understood pathogenesis of FTD and related dementias, and provide imaging markers to guide the development and assessment of new therapies.
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11C-PK-11195 has demonstrated selectivity for activated microglia over quiescent microglia and reactive astrocytes, relative insensitivity to common polymorphisms in TSPO compared to second generation TSPO ligands, and well established methods of non-invasive kinetic analysis.
“However, in favour of the use of 11C-PK-11195 is its demonstrated selectivity for activated microglia over quiescent microglia and reactive astrocytes (Banati, 2002), its relative insensitivity to common polymorphisms in TSPO compared to second generation TSPO ligands (Zhang, 2015; Stefaniak and O’Brien, 2016), and the fact that it has well established methods of non-invasive kinetic analysis (”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Zhang, 2015
TPSO signal increases with microglia activation in tauopathies including AD, PSP, PiD, and FTDP-17.
“TPSO signal has been shown to increase with microglia activation in tauopathies including AD, PSP, PiD, and FTDP-17 [111–113] as well as several other neurodegenerative diseases and injury models such as other frontotemporal dementias (FTDs), Parkinson’s disease, stroke and TBI [114].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [113]
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References 87 · Cited by 62
Research works printed but not linked: 3
- [5]Diehl-Schmid J Pohl C Perneczky R Hartmann J Förstl H Kurz A Frühsymptome, Überlebenszeit und Todesursachen. Initial symptoms, survival and causes of death in 115 patients with frontotemporal lobar degeneration Fortschr Neurol Psychiatr 2007 75 12 708 13 10.1055/s-2006-932201 16972211 · DOI
- [14]Jacobs AH Tavitian B INMiND consortium. Noninvasive molecular imaging of neuroinflammation J Cereb Blood Flow Metab 2012 32 7 1393 415 10.1038/jcbfm.2012.53 22549622 PMC3390799 · DOI · Paper page
- [44]Kreisl WC Lyoo CH McGwier M Snow J Jenko KJ Kimura N Biomarkers Consortium PET Radioligand Project Team. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease Brain 2013 136 Pt 7 2228 38 10.1093/brain/awt145 23775979 PMC3692038 · DOI · Paper page
- Authors
- Zhang, J.
- Affiliations
- Western University (CA)
- Corresponding author
- Zhang, Jing
- ORCID
- Zhang, Jing
- Venue
- Journal of Neuroinflammation
- Published
- 2015-05-29
- Volume
- 12
- Issue
- 1
- Pages
- 108-108
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC4451729
- OpenAlex
- W1586197955
- Cited by
- 62
- References
- 87
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 5 · 2014: 1
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- frontotemporal dementia, neuroinflammation, microglial activation, translocator protein (TSPO), TSPO PET imaging, [11C]PK11195, molecular imaging, neurodegenerative dementia, early detection, imaging biomarkers, therapeutic monitoring
- MeSH terms
- Brain Mapping, Encephalitis, Humans, Radiopharmaceuticals, Positron-Emission Tomography, Frontotemporal Dementia
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