Causal association between plasma inflammatory proteins and longitudinal brain atrophy: a bidirectional Mendelian...

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Systemic inflammation is increasingly recognized for its impact on brain health.
• Understanding the relationship between inflammatory markers and brain structure changes is crucial for neurodegenerative disease research.

Purpose of the Study:

• To investigate the potential causal associations between 91 plasma inflammatory proteins and 15 longitudinal brain structural changes.
• To explore bidirectional relationships between systemic inflammation and brain atrophy using Mendelian Randomisation.

Main Methods:

• Utilized large-scale genome-wide association study datasets for plasma proteins (N=14,824) and brain structure changes (N=15,640).
• Employed bidirectional Mendelian Randomisation analysis with inverse variance-weighted estimates.
• Conducted sensitivity analyses including MR-Egger intercept, Cochran's Q test, and leave-one-out analysis.

Main Results:

• No statistically significant causal relationships were found between the 91 inflammatory proteins and 15 brain structural phenotypes at a Bonferroni-corrected threshold (p < 1.83 × 10⁻⁵).
• Several nominal associations (p < 0.05) were identified in both forward (proteins to brain) and reverse (brain to proteins) analyses.
• Examples include associations between CCL20 and nucleus accumbens volume, MMP-1 and cortical thinning, and IL-15RA and ventricular enlargement.

Conclusions:

• While no strong causal links were established, nominal associations suggest potential bidirectional pathways between systemic inflammation and longitudinal brain structural changes.
• Alterations in plasma inflammatory proteins may contribute to changes in brain volume over time.
• These findings offer insights into the complex interplay between systemic inflammation and brain dynamics in neuroinflammatory processes.