Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study.
Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study.
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DOI：
10.1016/j.neurobiolaging.2019.12.004
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发表时间：
2020-04
影响因子：
4.2
通讯作者：
Kantarci K
中科院分区：
文献类型：
--
作者：
Chen Q;Boeve BF;Senjem M;Tosakulwong N;Lesnick T;Brushaber D;Dheel C;Fields J;Forsberg L;Gavrilova R;Gearhart D;Graff-Radford J;Graff-Radford N;Jack CR Jr;Jones D;Knopman D;Kremers WK;Lapid M;Rademakers R;Ramos EM;Syrjanen J;Boxer AL;Rosen H;Wszolek ZK;Kantarci K
蛋白前基因（GRN）的功能缺失突变是家族性额颞叶变性（FTLD）的主要原因之一。我们的目的是通过纵向结构MRI确定无症状和有症状的GRN突变携带者的脑叶皮质萎缩率和轨迹。本研究中的个体来自Mayo诊所的ADRC和LEFFTDS研究。我们确定了13例GRN突变携带者（8例无症状，5例有症状）和非携带者（n=10），他们至少有2次连续t1加权结构mri，每年随访，中位数为3年（1.0至9.8年）。采用基于张量的对称归一化形态学（TBM-SyN）算法分析脑叶皮质体积的纵向变化。采用线性混合效应模型模拟三组大脑皮层体积随时间的变化。无症状GRN突变携带者的额叶皮质萎缩（p<0.05）和顶叶皮质萎缩（p<0.01）年发生率高于非携带者。有症状的GRN突变携带者在额叶和顶叶皮层的萎缩率也高于非携带者（p<0.01）。此外，症状性GRN突变携带者的颞叶皮层萎缩率高于非携带者（p<0.001）。我们发现，在无症状的GRN突变携带者中，额叶和顶叶皮质体积下降，并在有症状的GRN突变携带者中继续下降，而只有在有症状的GRN突变携带者中，才观察到颞叶皮质萎缩率增加。在GRN突变携带者中，这种连续的皮层受累模式对于在涉及GRN突变携带者的潜在治疗试验中利用神经变性的成像生物标志物作为结果测量具有重要意义。
Loss-of-function mutations in the progranulin gene (GRN) are one of the major causes of familial frontotemporal lobar degeneration (FTLD). Our objective was to determine the rates and trajectories of lobar cortical atrophy from longitudinal structural MRI in both asymptomatic and symptomatic GRN mutation carriers. Individuals in this study were from the ADRC and LEFFTDS studies at the Mayo Clinic. We identified 13 GRN mutation carriers (8 asymptomatic, 5 symptomatic) and non-carriers (n=10) who had at least 2 serial T1-weighted structural MRIs and were followed annually with a median of 3 years (range 1.0 to 9.8 years). Longitudinal changes in lobar cortical volume were analyzed using the tensor-based morphometry with symmetric normalization (TBM-SyN) algorithm. Linear mixed effect models were used to model cortical volume change over time among 3 groups. The annual rates of frontal (p<0.05) and parietal (p<0.01) lobe cortical atrophy were higher in asymptomatic GRN mutation carriers than non-carriers. The symptomatic GRN mutation carriers also had increased rates of atrophy in the frontal (p<0.01) and parietal lobe (p<0.01) cortices than non-carriers. In addition, greater rates of cortical atrophy were observed in the temporal lobe cortices of symptomatic GRN mutation carriers than non-carriers (p<0.001). We found that a decline in frontal and parietal lobar cortical volume occurs in asymptomatic GRN mutation carriers and continues in the symptomatic GRN mutation carriers, while an increased rate of temporal lobe cortical atrophy is observed only in symptomatic GRN mutation carriers. This sequential pattern of cortical involvement in GRN mutation carriers has important implications for utilizing imaging biomarkers of neurodegeneration as an outcome measure in potential treatment trials involving GRN mutation carriers.
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DOI：
10.1093/brain/awx103
发表时间：
2017-06-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Premi E;Grassi M;van Swieten J;Galimberti D;Graff C;Masellis M;Tartaglia C;Tagliavini F;Rowe JB;Laforce R Jr;Finger E;Frisoni GB;de Mendonça A;Sorbi S;Gazzina S;Cosseddu M;Archetti S;Gasparotti R;Manes M;Alberici A;Cardoso MJ;Bocchetta M;Cash DM;Ourselin S;Padovani A;Rohrer JD;Borroni B;Genetic FTD Initiative (GENFI)
通讯作者：
Genetic FTD Initiative (GENFI)
DOI：
10.3233/jad-150270
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
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作者：
Caroppo P;Habert MO;Durrleman S;Funkiewiez A;Perlbarg V;Hahn V;Bertin H;Gaubert M;Routier A;Hannequin D;Deramecourt V;Pasquier F;Rivaud-Pechoux S;Vercelletto M;Edouart G;Valabregue R;Lejeune P;Didic M;Corvol JC;Benali H;Lehericy S;Dubois B;Colliot O;Brice A;Le Ber I;Predict-PGRN study group
通讯作者：
Predict-PGRN study group
DOI：
10.1016/s1474-4422(14)70324-2
发表时间：
2015-03
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Rohrer JD;Nicholas JM;Cash DM;van Swieten J;Dopper E;Jiskoot L;van Minkelen R;Rombouts SA;Cardoso MJ;Clegg S;Espak M;Mead S;Thomas DL;De Vita E;Masellis M;Black SE;Freedman M;Keren R;MacIntosh BJ;Rogaeva E;Tang-Wai D;Tartaglia MC;Laforce R Jr;Tagliavini F;Tiraboschi P;Redaelli V;Prioni S;Grisoli M;Borroni B;Padovani A;Galimberti D;Scarpini E;Arighi A;Fumagalli G;Rowe JB;Coyle-Gilchrist I;Graff C;Fallström M;Jelic V;Ståhlbom AK;Andersson C;Thonberg H;Lilius L;Frisoni GB;Pievani M;Bocchetta M;Benussi L;Ghidoni R;Finger E;Sorbi S;Nacmias B;Lombardi G;Polito C;Warren JD;Ourselin S;Fox NC;Rossor MN;Binetti G
通讯作者：
Binetti G
影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
4.2
作者：
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通讯作者：
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