title: Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD.
abstract: 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.
authors: Centre for Aging Brain and Neurodegenerative Disorder, Neurology Unit, University of Brescia, Brescia, Italy. bborroni@inwind.it
authors: Barbara
authors: B
authors: Borroni
authors: Antonella
authors: A
authors: Alberici
authors: Mara
authors: M
authors: Cercignani
authors: Enrico
authors: E
authors: Premi
authors: Laura
authors: L
authors: Serra
authors: Carlo
authors: C
authors: Cerini
authors: Maura
authors: M
authors: Cosseddu
authors: Carla
authors: C
authors: Pettenati
authors: Marinella
authors: M
authors: Turla
authors: Silvana
authors: S
authors: Archetti
authors: Roberto
authors: R
authors: Gasparotti
authors: Carlo
authors: C
authors: Caltagirone
authors: Alessandro
authors: A
authors: Padovani
authors: Marco
authors: M
authors: Bozzali
mesh_terms: D017668:Age of Onset; D000368:Aged; D001925:Brain Damage, Chronic / Q000235:genetics / Q000473:pathology; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009415:Nerve Net / Q000473:pathology; D009473:Neuronal Plasticity / Q000235:genetics; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins