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

被引:68
作者
Sudre, Carole H. [1 ,2 ]
Bocchetta, Martina [1 ]
Cash, David [1 ,2 ]
Thomas, David L. [1 ,2 ]
Woollacott, Ione [1 ]
Dick, Katrina M. [1 ]
van Swieten, John [3 ]
Borroni, Barbara [4 ]
Galimberti, Daniela [5 ]
Masellis, Mario [6 ,7 ]
Tartaglia, Maria Carmela [8 ]
Rowe, James B. [9 ]
Graff, Caroline [10 ,11 ,12 ]
Tagliavini, Fabrizio [13 ]
Frisoni, Giovanni [14 ]
Laforce, Robert, Jr. [15 ]
Finger, Elizabeth [16 ]
de Mendonca, Alexandre [17 ]
Sorbi, Sandro [18 ,19 ]
Ourselin, Sebastien [1 ,2 ]
Cardoso, M. Jorge [1 ,2 ]
Rohrer, Jonathan D. [1 ]
机构
[1] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, Queen Sq, London WC1N 3BG, England
[2] UCL, Ctr Med Image Comp, London, England
[3] Erasmus MC, Rotterdam, Netherlands
[4] Univ Brescia, Brescia, Italy
[5] Univ Milan, Dept Pathophysiol & Transplantat, Dino Ferrari Ctr, IRCCS Osped Maggiore Policlin,Fdn Ca Granda, Milan, Italy
[6] Sunnybrook Hlth Sci Ctr, Cognit Neurol Res Unit, Hurvitz Brain Sci Res Program, Sunnybrook Res Inst, Toronto, ON, Canada
[7] Univ Toronto, Dept Med, Toronto, ON, Canada
[8] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
[9] Univ Cambridge, Cambridge, England
[10] Karolinska Inst, Stockholm, Sweden
[11] Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Neurogeriatr, Stockholm, Sweden
[12] Karolinska Univ Hosp, Dept Geriatr Med, Stockholm, Sweden
[13] Ist Neurol Carlo Besta, Milan, Italy
[14] IRCCS San Giovanni di Dio Fatebenefratelli Bresci, Brescia, Italy
[15] Univ Laval, Quebec City, PQ, Canada
[16] Univ Western Ontario, London, ON, Canada
[17] Univ Lisbon, Fac Med, Lisbon, Portugal
[18] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy
[19] IRCCS Don Gnocchi, Florence, Italy
基金
英国工程与自然科学研究理事会; 加拿大健康研究院; 英国惠康基金; 欧盟第七框架计划; 英国医学研究理事会;
关键词
FRONTOTEMPORAL LOBAR DEGENERATION; LESIONS; SEGMENTATION; DEMENTIA;
D O I
10.1016/j.nicl.2017.04.015
中图分类号
R445 [影像诊断学];
学科分类号
100207 ;
摘要
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.
引用
收藏
页码:171 / 180
页数:10
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