Biomarkers of Neuroinflammation

Bain, Lisa J.; Keren, Noam I.; Norris, Sheena M. Posey

doi:10.17226/24854

Cited by 5 publications

(1 citation statement)

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“…Identification of inflammation as early as possible in the primary stages of the neurodegenerative process could enable early delivery of therapeutics, potentially in the prodromal phase of disease [39]. As agents that modulate neuroinflammation are being assessed in clinical trials in diseases such as ALS [59], monitoring neuroinflammation could assist in these trials by allowing tracking of disease progression and providing an indication of therapeutic response [27,60]. Furthermore, clinical trials could be streamlined to assist therapeutic efficacy, by providing insights into the underlying pathophysiology of neuroinflammatory and regulatory pathways [27,39,61].…”

Section: Neuroinflammation In Neurodegenerative Disordersmentioning

confidence: 99%

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

Werry

Bright

Piguet

et al. 2019

IJMS

203

159

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Neuroinflammation is an inflammatory response in the brain and spinal cord, which can involve the activation of microglia and astrocytes. It is a common feature of many central nervous system disorders, including a range of neurodegenerative disorders. An overlap between activated microglia, pro-inflammatory cytokines and translocator protein (TSPO) ligand binding was shown in early animal studies of neurodegeneration. These findings have been translated in clinical studies, where increases in TSPO positron emission tomography (PET) signal occur in disease-relevant areas across a broad spectrum of neurodegenerative diseases. While this supports the use of TSPO PET as a biomarker to monitor response in clinical trials of novel neurodegenerative therapeutics, the clinical utility of current TSPO PET radioligands has been hampered by the lack of high affinity binding to a prevalent form of polymorphic TSPO (A147T) compared to wild type TSPO. This review details recent developments in exploration of ligand-sensitivity to A147T TSPO that have yielded ligands with improved clinical utility. In addition to developing a non-discriminating TSPO ligand, the final frontier of TSPO biomarker research requires developing an understanding of the cellular and functional interpretation of the TSPO PET signal. Recent insights resulting from single cell analysis of microglial phenotypes are reviewed.

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Section: Neuroinflammation In Neurodegenerative Disordersmentioning

confidence: 99%

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

Werry

Bright

Piguet

et al. 2019

IJMS

203

159

View full text Add to dashboard Cite

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Biomarker Methodologies: A NIMH Perspective

Grabb,

Brady

2024

Advances in Neurobiology

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Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination

Lee

Sati

et al. 2018

Brain

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Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although it has been extensively studied, the proximate trigger of the immune response remains uncertain. Experimental autoimmune encephalomyelitis in the common marmoset recapitulates many radiological and pathological features of focal multiple sclerosis lesions in the cerebral white matter, unlike traditional experimental autoimmune encephalomyelitis in rodents. This provides an opportunity to investigate how lesions form as well as the relative timing of factors involved in lesion pathogenesis, especially during early stages of the disease. We used MRI to track experimental autoimmune encephalomyelitis lesions in vivo to determine their age, stage of development, and location, and we assessed the corresponding histopathology post-mortem. We focused on the plasma protein fibrinogen-a marker for blood-brain barrier leakage that has also been linked to a pathogenic role in inflammatory demyelinating lesion development. We show that fibrinogen has a specific spatiotemporal deposition pattern, apparently deriving from the central vein in early experimental autoimmune encephalomyelitis lesions <6 weeks old, and preceding both demyelination and visible gadolinium enhancement on MRI. Thus, fibrinogen leakage is one of the earliest detectable events in lesion pathogenesis. In slightly older lesions, fibrinogen is found inside microglia/macrophages, suggesting rapid phagocytosis. Quantification demonstrates positive correlation of fibrinogen deposition with accumulation of inflammatory cells, including microglia/macrophages and T cells. The peak of fibrinogen deposition coincides with the onset of demyelination and axonal loss. In samples from chronic multiple sclerosis cases, fibrinogen was found at the edge of chronic active lesions, which have ongoing demyelination and inflammation, but not in inactive lesions, suggesting that fibrinogen may play a role in sustained inflammation even in the chronic setting. In summary, our data support the notion that fibrinogen is a key player in the early pathogenesis, as well as sustained inflammation, of inflammatory demyelinating lesions.

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Biomarkers of Neuroinflammation

Cited by 5 publications

References 0 publications

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

Biomarker Methodologies: A NIMH Perspective

Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination

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