Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications.
Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications.
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DOI：
10.1136/jnnp-2021-326914
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Le Ber I
中科院分区：
文献类型：
--
作者：
Saracino D;Dorgham K;Camuzat A;Rinaldi D;Rametti-Lacroux A;Houot M;Clot F;Martin-Hardy P;Jornea L;Azuar C;Migliaccio R;Pasquier F;Couratier P;Auriacombe S;Sauvée M;Boutoleau-Bretonnière C;Pariente J;Didic M;Hannequin D;Wallon D;French Research Network on FTD/FTD-ALS;PREV-DEMALS and Predict-PGRN study groups;Colliot O;Dubois B;Brice A;Levy R;Forlani S;Le Ber I
神经丝轻链（NfL）是遗传性额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）的一种有前途的生物标志物。我们评估了对照组的血浆神经丝轻链（pNfL）水平，以及C9 orf 72和GRN队列从症状前到临床阶段的纵向轨迹。我们使用单分子阵列（SiMoA）分析了668个样本（352个基线和316个随访）的pNfL，这些样本包括C9 orf 72和GRN患者、症状前携带者（PS）和年龄在21至83岁之间的对照。他们在>2年的时间内进行了纵向评价，在此期间，4例PS成为前驱/症状。pNfL和临床遗传变量之间的关联，和纵向NfL的变化，进行了研究，使用广义和线性混合效应模型。使用尤登指数确定最佳截止点。对照组pNfL水平随年龄增加，从约5至约18 pg/mL（p<0.0001），随时间推移而进展（平均年化变化率（ARC）：+3.9%/年，p<0.0001）。患者表现出更高的水平和更大的纵向进展（ARC：+26.7%，p<0.0001），具有基因特异性轨迹。GRN患者的水平高于C9 orf 72（86.21 vs 39.49 pg/mL，p=0.014），进展率更高（ARC：+29.3% vs +24.7%; p=0.016）。在C9 orf 72患者中，水平与表型相关（ALS：71.76 pg/mL，FTD：37.16，精神病：15.3; p=0.003），在缓慢进展患者中显著较低（24.11，ARC：+2.5%; p=0.05）。PS中的平均ARC为+3.2%，前驱携带者为+7.3%。我们提出了将患者与对照组区分数十年的基因特异性截止值。本研究强调了基因特异性和年龄特异性参考对遗传性FTD/ALS临床和治疗试验的重要性。它支持重复pNfL测量的有用性，并将ARC视为疾病进展的预后标志物。 NCT 02590276和NCT 04014673。
Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages. We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index. pNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades. This study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression. NCT02590276 and NCT04014673.
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影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
DOI：
10.3233/jad-150270
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
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：
10.1136/jnnp-2020-324647
发表时间：
2021-05
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Kmetzsch V;Anquetil V;Saracino D;Rinaldi D;Camuzat A;Gareau T;Jornea L;Forlani S;Couratier P;Wallon D;Pasquier F;Robil N;de la Grange P;Moszer I;Le Ber I;Colliot O;Becker E;PREV-DEMALS study group
通讯作者：
PREV-DEMALS study group
影响因子：
4.8
作者：
Al Shweiki, M. H. D. Rami;Steinacker, Petra;Otto, Markus
通讯作者：
Otto, Markus
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