Transcriptomic and neurotransmitter correlates of structure and function spatial variations patterns in...

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• Spinocerebellar ataxia (SCA) presents with cortical structural and functional deficits.
• The precise biological mechanisms driving SCA pathogenesis are not fully understood.

Purpose of the Study:

• To investigate cortical alterations in SCA patients using advanced neuroimaging techniques.
• To identify molecular pathways and biological processes associated with SCA.

Main Methods:

• T1-weighted and resting-state functional MRI (fMRI) were used to assess cortical thickness and amplitude of low-frequency fluctuations (ALFF).
• Neurotransmitter system mapping and gene expression analysis (partial least squares regression, gene ontology) were performed.
• Convergent imaging-transcriptomic analysis integrated molecular and cellular data.

Main Results:

• Cortical thickness and ALFF changes are sensitive biomarkers for cortical impairment in SCA.
• Thickness alterations correlate with disruptions in cholinergic, serotonergic, and glutamatergic systems.
• ALFF changes are linked to toxin response and detoxification pathways, with gene expression enriched in astrocytes.

Conclusions:

• The study provides a unified, systems-level view of SCA by integrating imaging and transcriptomic data.
• Findings highlight molecular pathways and non-neuronal cellular targets (astrocytes) in SCA.
• This approach enables network-informed prediction of additional vulnerable brain regions.