Local vulnerability and global connectivity jointly shape neurodegenerative disease propagation
作者： Yahar Zeighami , Alain Dagher , Yvonne Yau , Kevin Larcher , Bratislav Misic
DOI: 10.1101/449199
关键词:
摘要: Abstract It is becoming increasingly clear that brain network organization shapes the course and expression of neurodegenerative diseases. Parkinson’s disease (PD) marked by progressive spread atrophy from midbrain to subcortical structures eventually, cerebral cortex. Recent discoveries suggest process involves misfolding prion-like propagation endogenous α-synuclein via axonal projections. However, mechanisms translate local “synucleinopathy” large-scale dysfunction remain unknown. Here we use an agent-based epidemic spreading model integrate structural connectivity, functional connectivity gene expression, predict sequential volume loss due neurodegeneration. The dynamic replicates spatial temporal patterning empirical in PD implicates substantia nigra as epicenter. We reveal a significant role for both connectome topology geometry shaping distribution atrophy. also demonstrates SNCA GBA transcription influence concentration regional vulnerability. Functional co-activation further amplifies set architecture expression. Altogether, these results support theory progression multifactorial depends on cell-to-cell misfolded proteins
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