Networks-mediated spreading of pathology in neurodegenerative diseases

Abstract

In addition to their basic anatomical and functional roles, brain connections are a relevant conduit for the spreading of pathological factors that cause disease. In this chapter, we focus on connectivity-mediated intra-brain disease propagation in neurodegeneration, and how advanced brain computational modeling can contribute to characterize and prevent such pathological processes. These advanced models have the potential to further clarify the underlying biological mechanisms in the neurodegenerative brain, including cell-cell spreading of misfolded proteins (amyloid, tau) and functional hyperactivity, and, importantly, the associated synergistic (causal) interactions among multiple pathological components (e.g., toxics proteins, vascular and metabolic dysregulation, structural atrophy). Finally, we show that, by characterizing each patient's multifactorial brain changes in response to potential therapeutic inputs, robust predictions of treatment response can be obtained, potentially accelerating the finding of effective disease-modifying agents at the individual level.