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White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort

Authors :
Carole H. Sudre
Martina Bocchetta
David Cash
David L. Thomas
Ione Woollacott
Katrina M. Dick
John van Swieten
Barbara Borroni
Daniela Galimberti
Mario Masellis
Maria Carmela Tartaglia
James B. Rowe
Caroline Graff
Fabrizio Tagliavini
Giovanni Frisoni
Robert Laforce, Jr
Elizabeth Finger
Alexandre de Mendonça
Sandro Sorbi
Sébastien Ourselin
M. Jorge Cardoso
Jonathan D. Rohrer
Christin Andersson
Silvana Archetti
Andrea Arighi
Luisa Benussi
Giuliano Binetti
Sandra Black
Maura Cosseddu
Marie Fallström
Carlos Ferreira
Chiara Fenoglio
Nick C. Fox
Morris Freedman
Giorgio Fumagalli
Stefano Gazzina
Roberta Ghidoni
Marina Grisoli
Vesna Jelic
Lize Jiskoot
Ron Keren
Gemma Lombardi
Carolina Maruta
Simon Mead
Lieke Meeter
Rick van Minkelen
Benedetta Nacmias
Linn Öijerstedt
Alessandro Padovani
Jessica Panman
Michela Pievani
Cristina Polito
Enrico Premi
Sara Prioni
Rosa Rademakers
Veronica Redaelli
Ekaterina Rogaeva
Giacomina Rossi
Martin N. Rossor
Elio Scarpini
David Tang-Wai
Hakan Thonberg
Pietro Tiraboschi
Ana Verdelho
Jason D. Warren
Source :
NeuroImage: Clinical, Vol 15, Iss , Pp 171-180 (2017)
Publication Year :
2017
Publisher :
Elsevier, 2017.

Abstract

Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.

Details

Language :
English
ISSN :
22131582
Volume :
15
Issue :
171-180
Database :
Directory of Open Access Journals
Journal :
NeuroImage: Clinical
Publication Type :
Academic Journal
Accession number :
edsdoj.89b4ebcd4f642b09beae4a74ef4772a
Document Type :
article
Full Text :
https://doi.org/10.1016/j.nicl.2017.04.015