Abstract
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 ([11C]-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.
Highlights
Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder, primarily affecting the frontal and/or temporal lobes of the brain
There are mainly three types of FTD: behavioral variant FTD, semantic dementia (SD), and progressive non-fluent aphasia (PNFA), and they are common in the aggregation of neuronal proteins such as the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein with molecular weight 43 kDa (TDP-43), and the fused in sarcoma protein (FUS) [3]
In its infancy, research on positron-emission tomography (PET) imaging with the second-generation translocator protein (TSPO) ligands is in progress and has shown increased uptake in brain regions associated with neuroinflammation in early FTD and other neurodegenerative disorders such as those of tau pathology, suggesting that TSPO imaging is useful in detecting neuroinflammation in vivo from the early stage of the disease
Summary
Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder, primarily affecting the frontal and/or temporal lobes of the brain. Postmortem immunohistochemistry study further demonstrated that compared with controls, higher level of microglial activation detected by [11C]-PK11195 was found in the frontal and temporal cortex in patients with FTD (n = 78), and greater microglial activation was found in the temporal subcortical white matter in FTD-MART than in other FTD genetic types [37] In neurodegenerative disorders such as FTD, there is a common pattern in the mechanisms of sensing abnormal protein aggregates, activating microglia, transducing to the release of cytokines, and amplifying the neurotoxic effects in a chronic inflammatory process [14]. In its infancy, research on PET imaging with the second-generation TSPO ligands is in progress and has shown increased uptake in brain regions associated with neuroinflammation in early FTD and other neurodegenerative disorders such as those of tau pathology (even at a presymptomatic stage), suggesting that TSPO imaging is useful in detecting neuroinflammation in vivo from the early stage of the disease
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