Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers.
Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers.
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DOI：
10.1002/acn3.559
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Lee SE
中科院分区：
文献类型：
--
作者：
Meeter LHH;Gendron TF;Sias AC;Jiskoot LC;Russo SP;Donker Kaat L;Papma JM;Panman JL;van der Ende EL;Dopper EG;Franzen S;Graff C;Boxer AL;Rosen HJ;Sanchez-Valle R;Galimberti D;Pijnenburg YAL;Benussi L;Ghidoni R;Borroni B;Laforce R Jr;Del Campo M;Teunissen CE;van Minkelen R;Rojas JC;Coppola G;Geschwind DH;Rademakers R;Karydas AM;Öijerstedt L;Scarpini E;Binetti G;Padovani A;Cash DM;Dick KM;Bocchetta M;Miller BL;Rohrer JD;Petrucelli L;van Swieten JC;Lee SE
评估poly(GP)，一种二肽重复蛋白和神经丝轻链（NfL）作为症状前C9orf72重复扩增携带者和C9orf72相关额颞叶痴呆患者的生物标志物。此外，探讨poly（GP）与神经退行性变指标（NfL、灰质体积）的关系。我们测量了25名症状前C9orf72扩张携带者、64名伴有痴呆的症状性扩张携带者和12名非携带者的脑脊液（CSF）中poly（GP）和NfL的水平。我们使用感兴趣区域和体素分析来探索与灰质体积的关联。Poly（GP）在C9orf72扩增携带者中存在，而在非携带者中不存在（特异性100%，敏感性97%）。症状前携带者poly（GP）水平低于症状前携带者。有症状携带者的NfL水平高于症状前携带者和健康非携带者。NfL在伴有运动神经元疾病的患者中最高，并与疾病严重程度和生存率相关。多聚（GP）水平与小灰质区域之间存在关联，但在多次比较校正后没有存在，而高水平的NfL与额颞顶皮层和丘脑的萎缩有关。C9orf72扩张携带者的研究表明：(1)GP水平区分症状前和症状性扩张携带者与非携带者，但与神经退行性变指标无关；(2) NfL水平与灰质萎缩、疾病严重程度和较短的生存期有关。总之，poly（GP）和NfL有望作为C9orf72相关额颞叶痴呆临床试验的互补生物标志物，其中poly（GP）作为靶标参与的潜在标志物，而NfL作为疾病活动和进展的标志物。
To evaluate poly(GP), a dipeptide repeat protein, and neurofilament light chain (NfL) as biomarkers in presymptomatic C9orf72 repeat expansion carriers and patients with C9orf72‐associated frontotemporal dementia. Additionally, to investigate the relationship of poly(GP) with indicators of neurodegeneration as measured by NfL and grey matter volume. We measured poly(GP) and NfL levels in cerebrospinal fluid (CSF) from 25 presymptomatic C9orf72 expansion carriers, 64 symptomatic expansion carriers with dementia, and 12 noncarriers. We explored associations with grey matter volumes using region of interest and voxel‐wise analyses. Poly(GP) was present in C9orf72 expansion carriers and absent in noncarriers (specificity 100%, sensitivity 97%). Presymptomatic carriers had lower poly(GP) levels than symptomatic carriers. NfL levels were higher in symptomatic carriers than in presymptomatic carriers and healthy noncarriers. NfL was highest in patients with concomitant motor neuron disease, and correlated with disease severity and survival. Associations between poly(GP) levels and small grey matter regions emerged but did not survive multiple comparison correction, while higher NfL levels were associated with atrophy in frontotemporoparietal cortices and the thalamus. This study of C9orf72 expansion carriers reveals that: (1) poly(GP) levels discriminate presymptomatic and symptomatic expansion carriers from noncarriers, but are not associated with indicators of neurodegeneration; and (2) NfL levels are associated with grey matter atrophy, disease severity, and shorter survival. Together, poly(GP) and NfL show promise as complementary biomarkers for clinical trials for C9orf72‐associated frontotemporal dementia, with poly(GP) as a potential marker for target engagement and NfL as a marker of disease activity and progression.
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影响因子：
16.2
作者：
Ash PE;Bieniek KF;Gendron TF;Caulfield T;Lin WL;Dejesus-Hernandez M;van Blitterswijk MM;Jansen-West K;Paul JW 3rd;Rademakers R;Boylan KB;Dickson DW;Petrucelli L
通讯作者：
Petrucelli L
影响因子：
9.9
作者：
Lu CH;Macdonald-Wallis C;Gray E;Pearce N;Petzold A;Norgren N;Giovannoni G;Fratta P;Sidle K;Fish M;Orrell R;Howard R;Talbot K;Greensmith L;Kuhle J;Turner MR;Malaspina A
通讯作者：
Malaspina A
影响因子：
5.7
作者：
Diedrichsen, Joern;Balsters, Joshua H.;Ramnani, Narender
通讯作者：
Ramnani, Narender
DOI：
10.1016/j.nicl.2016.12.006
发表时间：
2017
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Lee SE;Sias AC;Mandelli ML;Brown JA;Brown AB;Khazenzon AM;Vidovszky AA;Zanto TP;Karydas AM;Pribadi M;Dokuru D;Coppola G;Geschwind DH;Rademakers R;Gorno-Tempini ML;Rosen HJ;Miller BL;Seeley WW
通讯作者：
Seeley WW
DOI：
10.1016/j.dadm.2015.11.001
发表时间：
2015-12-01
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
Pijnenburg, Yolande A L;Verwey, Nicolaas A;Teunissen, Charlotte E
通讯作者：
Teunissen, Charlotte E