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Microglia Activation in Basal Ganglia Is a Late Event in Huntington Disease Pathophysiology

Natalia P Rocha1, Odelin Charron2, Leigh B Latham2

  • 1From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders (N.P.R.), Department of Neurology, McGovern Medical School, The University of Texas Health Science Center, Houston; Department of Neurology (O.C., L.F.), The University of Texas at Austin; School of Medicine (L.B.L.), University of Washington, Seattle; Neuropsychiatry Program (G.D.C., A.L.T.), Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston; Houston Methodist Research Institute and Weill Cornell Medicine (P.Z.-F., M.Y.), TX; and HDSA Center of Excellence at University of Texas Health Science Center at Houston (E.F.S.). npessoarocha@gmail.com.

Neurology(R) Neuroimmunology & Neuroinflammation
|April 2, 2021
PubMed
Abstract

Insights

Microglial activation is elevated in manifest Huntington's disease (HD) but not premanifest stages. This neuroinflammation correlates with disease progression and neurodegeneration in HD patients.

Area of Science:

  • Neuroscience
  • Immunology
  • Radiochemistry

Background:

  • Huntington's disease (HD) is a progressive neurodegenerative disorder.
  • The role of microglia, the brain's immune cells, in HD pathogenesis remains incompletely understood.
  • Assessing microglial activation is crucial for understanding HD progression and developing targeted therapies.

Purpose of the Study:

  • To investigate microglial activation across different stages of Huntington's disease (HD).
  • To correlate microglial activation with neurodegeneration and clinical features in premanifest and manifest HD.
  • To explore the functional capacity of microglia in vitro.

Main Methods:

  • Utilized Positron Emission Tomography (PET) with the TSPO radioligand [11C]-ER176 to quantify microglial activation.
  • Included 18 subjects: 6 controls, 6 premanifest HD, and 6 manifest HD gene carriers.
  • Correlated [11C]-ER176 binding (Standardized Uptake Value Ratio - SUVR) with MRI-derived volumes, disease burden, and clinical scores.

Main Results:

  • Manifest HD patients showed significantly higher [11C]-ER176 SUVR in the globi pallidi and putamina compared to controls.
  • No significant differences in microglial activation were found between premanifest HD and controls or manifest HD groups.
  • Increased microglial activation correlated with greater cumulative disease burden and reduced regional brain volumes.

Conclusions:

  • Microglial activation is a key component of Huntington's disease pathophysiology.
  • Elevated microglial activation is associated with disease progression and neurodegeneration in manifest HD.
  • In vitro studies showed no difference in phagocytic capacity of microglia-like cells across HD stages.

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