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

被引：91

作者：

Borroni, Barbara ^{[1
]}

Alberici, Antonella ^{[1
]}

Cercignani, Mara ^{[2
]}

Premi, Enrico ^{[1
]}

Serra, Laura ^{[2
]}

Cerini, Carlo ^{[1
]}

Cosseddu, Maura ^{[1
]}

Pettenati, Carla ^{[3
]}

Turla, Marinella ^{[4
]}

Archetti, Silvana ^{[5
]}

Gasparotti, Roberto ^{[6
]}

Caltagirone, Carlo ^{[7
,8
]}

Padovani, Alessandro ^{[1
]}

Bozzali, Marco ^{[2
]}

机构：

[1] Univ Brescia, Ctr Aging Brain & Neurodegenerat Disorder, Neurol Unit, I-25125 Brescia, Italy

[2] Santa Lucia Fdn IRCCS, Neuroimaging Lab, I-00179 Rome, Italy

[3] Alzheimers Ctr, Milan, Italy

[4] ValleCamon Hosp, Neurol Unit, Brescia, Italy

[5] Brescia Hosp, Lab Biotechnol 3, Brescia, Italy

[6] Univ Brescia, Neuroradiol Unit, I-25125 Brescia, Italy

[7] Santa Lucia Fdn, Dept Clin & Behav Neurol, IRCCS, Rome, Italy

[8] Univ Roma Tor Vergata, Dept Neurosci, Rome, Italy

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 10期

关键词：

Progranulin; Granulin; Frontotemporal lobar degeneration; Preclinical; Voxel based morphometry; Resting state fMRI; FRONTOTEMPORAL LOBAR DEGENERATION; PROGRANULIN GENE-MUTATIONS; RESTING STATE NETWORKS; ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; DEMENTIA; TAU; VARIABILITY; INVENTORY; PHENOTYPE;

D O I：

10.1016/j.neurobiolaging.2011.10.031

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

030301 [社会学]; 100201 [内科学];

摘要：

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. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：2506 / 2520

页数：15

共 53 条

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The Frontal Behavioural Inventory (Italian version) differentiates frontotemporal lobar degeneration variants from Alzheimer's disease [J].