Spatial gene expression and functional network abnormalities in multiple sclerosis: exploring biological influence on
Paolo Preziosa1,2,3, Matteo Azzimonti1, Loredana Storelli1
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Translational Psychiatry
|March 3, 2026
Summary
This study links multiple sclerosis (MS) brain network changes to specific gene expressions, revealing biological factors influencing disease progression and cognitive impairment. Understanding these links can guide future MS treatments.
Area of Science:
- Neuroscience
- Genomics
- Medical Imaging
Background:
- Multiple Sclerosis (MS) is characterized by functional network abnormalities linked to accumulating structural damage.
- The biological basis and spatial distribution of these MS-related functional network abnormalities remain unclear.
- Investigating the interplay between gene expression and brain network alterations is crucial for understanding MS pathophysiology.
Purpose of the Study:
- To investigate the associations between MS-related functional network abnormalities and physiological gene expression.
- To identify specific genes and biological pathways correlating with altered brain network topography in MS patients.
- To explore differences in gene expression and network alterations across MS subtypes and cognitive statuses.
Main Methods:
- Utilized resting-state functional MRI (fMRI) to generate degree centrality maps in 558 MS patients and 214 healthy controls (HC).
- Correlated functional network centrality abnormalities with gene expression data from the Allen Human Brain Atlas (AHBA).
- Performed pathway enrichment analysis on significantly associated genes using the Multimodal Environment for Neuroimaging and Genomic Analysis.
Main Results:
- MS patients exhibited altered centrality in the default-mode network (DMN) and salience network/cerebellum compared to HC, associated with immune and cytokine-related genes.
- Progressive MS showed increased centrality in DMN and cerebellum, linked to epigenetic and mitochondrial genes, versus relapsing-remitting MS.
- Cognitively impaired MS patients displayed higher centrality in DMN and mesial temporal lobe, negatively correlated with DNASE1 and CP gene expression.
Conclusions:
- Physiological regional gene expression spatially correlates with functional network alterations observed in multiple sclerosis.
- Biological factors, including inflammation, immune response, epigenetic, and mitochondrial functions, may influence regional vulnerability or resilience in MS.
- Specific gene expression patterns are associated with cognitive impairment in MS, potentially implicating DNA degradation and iron homeostasis.
