Differing mechanisms drive regional tau distribution and load in Alzheimer's disease

Brisbane Convention & Exhibition Centre 

Tau pathology is a hallmark of Alzheimer's disease (AD), spreading through the brain in specific patterns likely driven by brain connectivity (Liu et al., 2012; Walsh et al., 2016). Accumulating evidence suggests that certain brain regions are more susceptible to tau accumulation due to cellular composition, gene expression, receptor profiles, developmental patterns, or pathological conditions (Brettschneider et al., 2015; Mrdjen et al., 2019). However, most computational models simulating tau propagation focus on connectome-based spreading only, often constrained to specific connectivity types (Vogel et al., 2020; Yang et al., 2021), with limited exploration of regional vulnerability (Anand et al., 2022). We used the Susceptible-Infected-Removed (SIR) agent-based model (Zheng et al., 2019), a connectome-based spreading model integrating regional biological properties to modulate tau spread. Using diverse brain connectomes and regional biological measures, we aimed to investigate whether tau propagation is driven by connectome-based spreading, regional vulnerability, or their interplay.