Neuroinflammation in Huntington’s Disease: New Insights with 11 C-PBR28 PET/MRI
Abstract
Huntington’s disease is a devastating neurodegenerative genetic disorder that causes progressive motor dysfunction, emotional disturbances, and cognitive impairment. Unfortunately, there is no treatment to cure or slow the progression of the disease. Neuroinflammation is one hallmark of Huntington’s disease, and modulation of neuroinflammation has been suggested as a potential target for therapeutic intervention. The relationship between neuroinflammation markers and the disease pathology is still poorly understood. To improve our understanding of neuroinflammation in Huntington’s disease, we measured translocator protein (TSPO) expression using 11 C-PBR28 and simultaneous PET/MRI. Standardized-uptake-value ratios, normalized by whole brain uptake, were calculated for data acquired 60–90 min after radiotracer administration. We identified distinct patterns of regional neuroinflammation (as defined by TSPO overexpression relative to a control group) in the basal ganglia of Huntington’s disease patients. These patterns were observed at the individual level in all patients, with region of interest analysis confirming significant differences between patients and the control group in the putamen and the pallidum. Additionally, we observed further distinct regional and subregional signatures, which may provide insights into phenotypical variability. For example, in certain Huntington’s disease patients, we observed in vivo elevation of the level of TSPO binding in subnuclei in the thalamus and brainstem that have been previously associated with visual function, motor function, and motor coordination. Our main result is an objective score, based solely on 11 C-PBR28 measurements, that correlates well with measurements of brain atrophy. We conclude that PET/MR imaging using 11 C-PBR28 provides a high signal-to-background ratio and has the potential to be used to assess Huntington’s disease progression. Our results suggest 11 C-PBR28 might prove useful in clinical trials evaluating therapies targeting neuroinflammation.
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Neuroinflammation is closely related to neurodegenerative diseases, such as Huntington's, Alzheimer's and Parkinson's disease, and neuropsychiatric disorders, such as major depressive disorder, bipolar disorder and anxiety.
“In fact, neuroinflammation is closely related to neurodegenerative diseases, as Huntington’s [133], Alzheimer’s [134] and Parkinson’s disease [135] and neuropsychiatric disorders, such as major depressive disorder, bipolar disorder and anxiety [136].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [133]
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- Authors
- Lois, C., González, I., Izquierdo-García, D., Zürcher, N. R., Wilkens, P., Loggia, M. L., Hooker, J. M., & Rosas, H. D.
- Affiliations
- Harvard University (US)
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States
- Corresponding author
- Lois, Cristina
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-05-02
- Volume
- 9
- Issue
- 11
- Pages
- 2563-2571
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W2801506064
- Cited by
- 84
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 15 · 2023: 14 · 2022: 13 · 2021: 14 · 2020: 14 · 2019: 1 · 2018: 1
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy (DE-SC0008430)
- National Institutes of Health (NS042861)
- Madrid-MIT M+Vision Consortium
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Huntington's disease, neuroinflammation, translocator protein (TSPO), [11C]PBR28, PET/MRI, basal ganglia, putamen, globus pallidus, brain atrophy, disease progression, neuroinflammation biomarkers, thalamus, brainstem
- MeSH terms
- Acetamides, Aged, Astrocytes, Brain, Carbon Radioisotopes, Female, Globus Pallidus, Humans, Huntington Disease, Inflammation, Magnetic Resonance Imaging, Male, Middle Aged, Putamen, Pyridines, Thalamic Nuclei, Case-Control Studies, Microglia, Receptors, GABA, Disease Progression, Radiopharmaceuticals, Positron-Emission Tomography, Multimodal Imaging
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