Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia.

Area of Science:

• Neuroscience
• Neuroimaging
• Genetics

Background:

• Brain connections facilitate the spread of neurodegeneration.
• Atrophy patterns in behavioral variant of frontotemporal dementia (bvFTD) are not fully understood in relation to brain network organization.

Purpose of the Study:

• To investigate how the brain's connectome architecture influences neurodegeneration patterns in sporadic and genetic bvFTD.
• To identify the primary brain regions affected by atrophy in bvFTD.

Main Methods:

• Regional atrophy patterns were analyzed in genetic and sporadic bvFTD patient cohorts.
• Structural and functional connectivity data were used to model atrophy spread.
• Data-driven and simulation-based methods identified atrophy epicenters.

Main Results:

• Atrophy patterns in bvFTD primarily affect the limbic network and insula.
• Regional atrophy strongly correlated with connected neighboring regions, confirming network influence.
• The anterior insula was identified as the main epicentre of atrophy, with secondary involvement in frontal and temporal areas.
• FTD-related genes (C9orf72, TARDBP) contribute to local vulnerability and disease propagation.

Conclusions:

• Connectome architecture and local transcriptomic vulnerability jointly shape bvFTD atrophy patterns.
• This explains how diverse pathologies can result in the same clinical syndrome.