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

Abstract

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.

Cognitive Dysfunction in Systemic Lupus Erythematosus: A Case for Initiating Trials

“…Therefore, clinical trials that employ imaging as an outcome measure based on a plausible pathogenic mechanism, such as DNRAb‐mediated neurotoxicity and microglial activation, may be advantageous before moving onto larger clinical trials with cognitive testing. Several longitudinal studies of TSPO‐PET in AD reveal increased microglial activation over time, and in one study it correlated with worsening CD . These results suggest that TSPO‐PET imaging may apply as a biomarker of CD in SLE.…”

“…Alzheimer's disease (AD), there is compelling evidence for an association between TSPO overexpression in disease-specific brain regions and poor cognitive performance (24). In SLE, only one neuroimaging study using the TSPO ligand has been performed, revealing higher TPSO expression in the cerebellum and hippocampus in those with CD compared to those without (25).…”

“…PET tracers targeting TSPO have shown that it is expressed on the outer mitochondrial membrane of microglia and is markedly up‐regulated in response to brain injury and inflammation. In several neurodegenerative diseases, including Alzheimer's disease (AD), there is compelling evidence for an association between TSPO overexpression in disease‐specific brain regions and poor cognitive performance . In SLE, only one neuroimaging study using the TSPO ligand has been performed, revealing higher TPSO expression in the cerebellum and hippocampus in those with CD compared to those without .…”

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

“…Recently, several targets have been investigated for PET imaging of neuroinflammation [11][12][13][14][15][16][17][18]. Specifically, multiple PET tracers binding the 18-kDa translocator protein (TSPO) have been evaluated in psychiatric [1] and neurodegenerative disorders [2,19,20]. There was limited success [21][22][23][24], but also failures [25][26][27][28][29][30].…”

Therapeutic strategies for glucose transporter 1 deficiency syndrome

“…In the absence of human autopsy material to investigate such pathology, imaging techniques may prove instructive. Thus, for instance, the microvasculature could potentially be examined using arterial spin labeling to measure cerebral perfusion, while the extent of neuroinflammation may be gleaned by exploiting PET imaging and ligands such as 11 C‐PK11195 and 11 C‐deuterium‐l‐deprenyl which bind the microglial translocator protein and astrocytic monoamine oxidase B proteins respectively . We are exploring each of these in model mice as well as in the human patient in present work.…”