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Updated: Sep 12, 2025
08:59
Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
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Network spreading and local biological vulnerability in amyotrophic lateral sclerosis
Asa Farahani1, Justine Y Hansen1, Vincent Bazinet1
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada.
Communications Biology
|August 4, 2025
Summary
Amyotrophic Lateral Sclerosis (ALS) pathology spreads through brain networks and local vulnerability. Motor cortex regions with specific metabolic profiles and mitochondrial functions are disease epicenters, impacting patient symptoms.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Systems Biology
Background:
- Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting the motor system.
- Pathology spread is influenced by local neuronal vulnerability and brain network connectivity.
- The interplay between local vulnerability and network spreading in shaping cortical atrophy remains unclear.
Purpose of the Study:
- To investigate how brain network structure and local biological features interact to shape cortical atrophy patterns in ALS.
- To identify the spatial distribution and biological underpinnings of disease epicenters in ALS.
Main Methods:
- Analysis of the Canadian ALS Neuroimaging Consortium (CALSNIC) dataset.
- Estimation of cortical atrophy using deformation-based morphometry (DBM).
- Transcriptomic analysis to identify enriched biological processes at disease epicenters.
Main Results:
- Cortical atrophy patterns in ALS align with structural brain connectivity.
- Atrophy is more prevalent in regions with similar metabolic profiles.
- Disease epicenters are primarily located in the motor cortex.
- Epicenter regions show enrichment for mitochondrial function and support cell-related genes (endothelial cells, pericytes).
- Individual differences in epicenter location correlate with clinical and cognitive symptoms, defining patient subtypes.
Conclusions:
- Network structure and local biological features are critical determinants of cortical atrophy spatial patterning in ALS.
- Motor cortex, particularly regions with specific metabolic and cellular profiles, serves as a key disease epicenter.
- Understanding these spatial dynamics offers insights into ALS progression and potential patient stratification.
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