title: White matter hyperintensities characterize monogenic frontotemporal dementia with granulin mutations.
abstract: No study but one has suggested the presence of white matter hyperintensities (WMHs) in frontotemporal dementia (FTD), limited to 4 cases carrying pathogenic Granulin (GRN) gene mutations. We investigated the presence of WMHs in a cohort of 14 FTD patients with pathogenic GRN mutations (GRN+), 28 patients without GRN mutations (GRN-) and 18 healthy controls (HC). We further considered 11 asymptomatic GRN+ subjects and 11 young age-matched healthy controls (yHC). The WMH burden was automatically computed and a voxelwise-based analysis was carried out to explore the differences in WMH brain spatial distribution. FTD-GRN+ patients had increased total WMH burden than both HC (p < 0.001) and FTD-GRN-(p = 0.01) groups. WMHs were mainly localized in the right middle frontal and superior temporal gyri, in the left superior frontal in the left parietal gyri. No significant differences of WMH burden between asymptomatic GRN+ and yHC were observed. The presence of WMHs in cases of FTD may suggest a novel mechanism of GRN disease-related neurodegeneration, may be of help in the differential diagnosis, and in guiding genetic screening.
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Biomedical Sciences and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Paternicò
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gazzina
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Cosseddu
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Alberici
authors.affiliation: The III Laboratory, Biotechnology, Spedali Civili Hospital, Brescia, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Cotelli
authors.affiliation: Casa di Cura San Francesco, Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Micheli
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Turla
authors.affiliation: The Neuroradiology Unit, University of Brescia, Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Electronic address: bborroni@inwind.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009410:Nerve Degeneration; D000077153:Progranulins; D066127:White Matter / Q000473:pathology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Asymptomatic; Frontotemporal dementia; Granulin; MRI; VBM; WMH