Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Barbara Borroni, Antonella Alberici, Mara Cercignani, Enrico Premi, Laura Serra, Carlo Cerini, Maura Cosseddu, Carla Pettenati, Marinella Turla, Silvana Archetti, Roberto Gasparotti, Carlo Caltagirone, Alessandro Padovani, Marco Bozzali

Research output: Contribution to journalArticlepeer-review


Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.

Original languageEnglish
Pages (from-to)2506-2520
Number of pages15
JournalNeurobiology of Aging
Issue number10
Publication statusPublished - Oct 2012


  • Frontotemporal lobar degeneration
  • Granulin
  • Preclinical
  • Progranulin
  • Resting state fMRI
  • Voxel based morphometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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