Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study
Open accessAbstract
Huntington's disease (HD) is an inherited neurodegenerative disorder associated with motor, cognitive and psychiatric deficits. This study, using a multimodal imaging approach, aims to assess in vivo the functional and structural integrity of regions and regional networks linked with motor, cognitive and psychiatric function. Predicting disease onset in at risk individuals is problematic and thus we sought to investigate this by computing the 5‐year probability of HD onset (p5 HD) and relating it to imaging parameters. Using MRI, 11 C‐PK11195 and 11 C‐raclopride PET, we have investigated volumes, levels of microglial activation and D2/D3 receptor binding in CAG repeat‐matched groups of premanifest and symptomatic HD gene carriers. Findings were correlated with disease‐burden and UHDRS scores. Atrophy was detected in sensorimotor striatum (SMST), substantia nigra, orbitofrontal and anterior prefrontal cortex in the premanifest HD. D2/D3 receptor binding was reduced and microglial activation increased in SMST and associative striatum (AST), bed nucleus of the stria terminalis, the amygdala and the hypothalamus. In symptomatic HD cases this extended to involve atrophy in globus pallidus, limbic striatum, the red nuclei, anterior cingulate cortex, and insula. D2/D3 receptor binding was additionally reduced in substantia nigra, globus pallidus, limbic striatum, anterior cingulate cortex and insula, and microglial activation increased in globus pallidus, limbic striatum and anterior prefrontal cortex. In premanifest HD, increased levels of microglial activation in the AST and in the regional network associated with cognitive function correlated with p5 HD onset. These data suggest that pathologically activated microglia in AST and other areas related to cognitive function, maybe better predictors of clinical onset and stresses the importance of early cognitive assessment in HD. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
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Dysregulation of microglia functions contributes to the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
“Dysregulation of microglia functions contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) (6–8), Parkinson’s disease (PD) (9–12) and Huntington’s disease (HD) (13–15).”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [14]
Huntington's disease involves a reactive microglial response and inflammation.
“Huntington's disease is associated with a reactive microglial response and consequent inflammation.”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Politis et al., 2011
In Huntington's disease, microglial activation is detected years before clinical symptom onset and correlates with striatal neuron dysfunction in subclinical and clinical stages.
“In Huntington's disease, microglial activation is detected years before the onset of clinical symptoms and correlates with striatal neuron dysfunction in subclinical (Tai et al. , 2007) as well as clinical stages of the disease (Pavese et al. , 2006; Politis et al. , 2011).”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Politis et al., 2011
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References 38 · Cited by 212
- Authors
- Politis, M., Pavese, N., Tai, Y. F., Kiferle, L., Mason, S. L., Brooks, D. J., Tabrizi, S. J., Barker, R. A., & Piccini, P.
- Affiliations
- Hammersmith Hospital (GB)
- University of Cambridge (GB)
- UCL Queen Square Institute of Neurology (GB)
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2011-01-13
- Volume
- 32
- Issue
- 2
- Pages
- 258-270
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6870088
- OpenAlex
- W2106708530
- Cited by
- 212
- References
- 38
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 16 · 2023: 14 · 2022: 15 · 2021: 16 · 2020: 8 · 2019: 10 · 2018: 14 · 2017: 17 · 2016: 18 · 2015: 17 · 2014: 20 · 2013: 17 · 2012: 14
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Huntington's disease, microglial activation, disease onset prediction, premanifest Huntington's disease, [11C]PK11195 PET, [11C]raclopride PET, sensorimotor striatum, associative striatum, brain atrophy, cognitive function, CAG repeat, gene carriers
- MeSH terms
- Adult, Brain, Brain Mapping, Cognition Disorders, Female, Humans, Huntington Disease, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Statistics as Topic, Microglia, Statistics, Nonparametric, Trinucleotide Repeat Expansion, Positron-Emission Tomography
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