Propagation of pathology through brain networks in neurodegenerative diseases: from molecules to clinical phenotypes

The cellular mechanisms underlying the stereotypical progression of pathology in neurodegenerative diseases are incompletely understood, but increasing evidence indicates that misfolded protein aggregates can spread by a self-perpetuating neuron-to-neuron transmission. Novel neuroimaging techniques can help elucidating how these disorders spread across brain networks. Recent knowledge from structural and functional connectivity studies suggests that the relation between neurodegenerative diseases and distinct brain networks is likely to be a strict consequence of diffuse network dynamics. Diffusion tensor magnetic resonance imaging also showed that measurement of white matter tract involvement can be a valid surrogate to assess the in vivo spreading of pathological proteins in these conditions. This review will introduce briefly the main molecular and pathological substrates of the most frequent neurodegenerative diseases and provide a comprehensive overview of neuroimaging findings that support the "network-based neurodegeneration" hypothesis in these disorders. Characterizing network breakdown in neurodegenerative diseases will help anticipate and perhaps prevent the devastating impact of these conditions.