Marco Bozzali1, Mara Cercignani1,
Antonella Alberici2, Enrico Premi2, Laura Serra1,
Carlo Cerini2, Maura Cosseddu2, Carla Pettenati2,
Santa Lucia Foundation,
Progranulin (PGRN) mutations have been recognized as monogenic causes of frontotemporal lobar degeneration (FTLD). However, their effect on brain tissue dysfunction/damage is poorly understood. Here, using voxel-based morphometry and resting-state fMRI, we investigated pre-symptomatic carriers and patients with FTLD with the same PGRN mutation. We show that PRGN mutation is an independent contributor to GM loss in FTLD. Using RS-fMRI, we show both, processes of disruption and reorganisation in specific networks, the latter being present since the preclinical stage of asymptomatic carriers . Again, the balance between functional disconnection and reorganization is unfavourable for FTLD patients carrying PRGN mutation.