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

Borroni, Barbara, Alberici, Antonella, Cercignani, Mara, Premi, Enrico, Serra, Laura, Cerini, Carlo, Cosseddu, Maura, Pettenati, Carla, Turla, Marinella, Archetti, Silvana, Gasparotti, Roberto, Caltagirone, Carlo, Padovani, Alessandro and Bozzali, Marco (2012) Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD. Neurobiology of Aging, 33 (10). pp. 2506-2520. ISSN 1558-1497

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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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Mara Cercignani
Date Deposited: 18 Oct 2012 09:17
Last Modified: 26 Sep 2017 13:09
URI: http://sro.sussex.ac.uk/id/eprint/41268
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