Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

Area of Science:

• Neuroimaging
• Neurology
• Molecular Imaging

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
• Understanding the relationship between neuroinflammation and structural brain changes in ALS is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the association between glial activation and brain structural abnormalities in individuals with ALS.
• To compare imaging findings in ALS patients with those in healthy controls.

Main Methods:

• Utilized integrated MR/PET imaging with the radioligand [11C]-PBR28 in 10 ALS patients and 10 controls.
• Performed Diffusion Tensor Imaging (DTI) for white matter integrity and surface-based analysis for cortical thickness.
• Correlated DTI metrics (FA, diffusivities) and cortical thickness with [11C]-PBR28 uptake in specific brain regions.

Main Results:

• Reduced fractional anisotropy (FA) and cortical thinning were observed in regions with higher [11C]-PBR28 binding in ALS patients.
• Significant correlations were found between [11C]-PBR28 binding, FA, and cortical thickness in the motor cortex.
• Upper Motor Neuron Burden (UMNB) scores correlated with glial activation, FA, and cortical thickness in the motor cortex.

Conclusions:

• Increased glial activation, indicated by [11C]-PBR28 uptake, colocalizes with structural brain changes in ALS.
• Findings suggest a link between neuroinflammation (gliosis) and structural alterations in both gray and white matter in ALS.
• This multimodal neuroimaging study provides an in vivo model for investigating ALS pathogenesis.