Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson's Disease

Area of Science:

• Neuroscience
• Genomics
• Biochemistry

Background:

• Cortical atrophy is a hallmark of advanced Parkinson's disease (PD).
• Understanding the molecular basis of cortical thickness changes is crucial for PD research.

Purpose of the Study:

• To investigate the relationship between gene expression in the healthy brain and cortical thickness variations in Parkinson's disease.
• To identify molecular pathways associated with cortical atrophy and hypertrophy in PD.

Main Methods:

• Integrated analysis of healthy brain transcriptomic data (Allen Human Brain Atlas) and MRI-derived cortical thickness from PD patients and controls.
• Partial least squares regression to correlate gene expression patterns with cortical thickness changes and clinical PD domains.

Main Results:

• Genes associated with cortical thickness changes in PD are enriched in cellular maintenance pathways: sumoylation, mitotic cell cycle regulation, mitochondrial translation, DNA damage response, and ER-Golgi traffic.
• Most pathways showed higher gene expression in atrophied cortical regions (negative correlation), while sumoylation pathways were upregulated in thickened regions (positive correlation).

Conclusions:

• Alterations in cellular maintenance mechanisms, including sumoylation and DNA repair, are implicated in cortical thickness changes in Parkinson's disease.
• These molecular changes may influence both motor and cognitive deficits observed in PD.