PRGN Mutation Modulates Brain Damage & Reorganization from Preclinical to Symptomatic Stages of Frontotemporal Dementia

Marco Bozzali¹, Mara Cercignani¹, Antonella Alberici², Enrico Premi², Laura Serra¹, Carlo Cerini², Maura Cosseddu², Carla Pettenati², Marina Turla², Silvana Archetti², Roberto Gasparotti², Alessandro Padovani², Barbara Borroni²

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.