A cell-level protein aggregation model reveals the main molecular mechanisms in neurodegenerative diseases

The molecular mechanisms that cause protein aggregation, which increases across the brain as neurodegenerative diseases like Alzheimer's disease progress, are still not well understood despite decades of research. Here, we propose a new approach by developing a reductionist, minimal, cell-level model to describe aggregation patterns in diseased brains. The model incorporates two general mechanisms driving aggregate formation: cell-autonomous triggers and cell-to-cell propagation. We introduce several measures to quantify protein aggregation dynamics and demonstrate that, under limiting regimes, our discrete model can be approximated by a continuous one. Finally, we show that our model matches disease patterns well across all proposed measures. Our mechanism-specific, high spatiotemporal resolution model provides strong predictive power for disease progression and suggests potential therapeutic interventions.