Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study.
Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study.
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DOI：
10.1016/s1474-4422(21)00129-0
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Fortea J
中科院分区：
文献类型：
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作者：
Carmona-Iragui M;Alcolea D;Barroeta I;Videla L;Muñoz L;Van Pelt KL;Schmitt FA;Lightner DD;Koehl LM;Jicha G;Sacco S;Mircher C;Pape SE;Hithersay R;Clare ICH;Holland AJ;Nübling G;Levin J;Zaman SH;Strydom A;Rebillat AS;Head E;Blesa R;Lleó A;Fortea J
我们试图验证血浆神经丝光 (NfL) 的临床效用、其预后价值以及唐氏综合症成人多中心队列的纵向变化。我们对患有唐氏综合症的成年人进行了纵向随访，并收集了来自六个中心的至少两份血浆样本。参与者被分类为无症状、前驱阿尔茨海默病或阿尔茨海默病痴呆，对生物标志物数据视而不见。我们将那些在随访期间沿着阿尔茨海默病连续体进展的个体归类为“进展者”。使用 Simoa SR-X™ 的商业套件测量血浆 NfL 水平。我们使用方差分析来评估基线 NfL 水平的差异，使用 Cox 回归来研究其预后价值，并使用线性混合模型来估计纵向变化。我们分析了 226 名唐氏综合症参与者的 572 个样本（165 名无症状患者 (70%)、32 名前驱阿尔茨海默病患者 (14%) 和 29 名阿尔茨海默病痴呆患者 (12%)）。平均随访时间为 3·6 (SD 1·6) 年。基线血浆 NfL 水平显示 ROC 曲线下面积分别为 0·83 (95% CI 0·76–0·91) 和 0·94 (95% CI 0·90–0·97)，用于区分无症状参与者与前驱组和痴呆组的参与者。基线 NfL 水平增加 1pg/ml 与临床进展风险增加 1·04 倍相关（95%CI 1·02–1·07）。血浆 NfL 调整水平在非进展者中保持稳定，但在无症状进展者组中每年增加 2·3 pg/ml (0·8–3·9)，在前驱阿尔茨海默病进展者中每年增加 3·3 pg/ml (1·6–4·9)，在患有阿尔茨海默病痴呆的参与者中每年增加 6·5 pg/ml (3·2–9·8 pg/ml)。血浆 NfL 水平对于唐氏综合症中症状性阿尔茨海默病的诊断具有出色的诊断和预后性能。血浆 NfL 的纵向轨迹使其能够在临床试验中用作治疗诊断标记。 AC Immune、La Caixa 基金会、Instituto de Salud Carlos III、国家老龄化研究所、Wellcome Trust、Jerome Lejeune 基金会、医学研究委员会、NIHR、JPND、阿尔茨海默氏症协会、DFG、VERUM。
We sought to validate the clinical utility of plasma Neurofilament light (NfL), its prognostic value, and the longitudinal changes in a multicentre cohort of adults with Down syndrome. We included adults with Down syndrome with longitudinal follow-up and at least two plasma samples from six centres. Participants were classified as asymptomatic, prodromal Alzheimer’s disease, or Alzheimer’s disease dementia, blind to biomarker data. We classified as “Progressors” those individuals that progressed along the Alzheimer’s continuum during the follow up. Plasma NfL levels were measured using commercial kits for the Simoa SR-X™. We performed ANOVA to evaluate differences in baseline NfL levels, Cox regression to study their prognostic value, and linear mixed models to estimate longitudinal changes. We analysed 572 samples from 226 participants with Down syndrome (165 asymptomatic (70%), 32 prodromal Alzheimer’s (14%), and 29 Alzheimer’s dementia (12%)). Mean follow-up was 3·6 (SD 1·6) years. Baseline plasma NfL levels showed an area under the ROC curve of 0·83 (95%CI 0·76–0·91) and 0·94 (95%CI 0·90–0·97) in differentiating asymptomatic participants from those in the prodromal and dementia groups, respectively. An increase in 1pg/ml in baseline NfL levels was associated to 1·04-fold risk of clinical progression (95%CI 1·02–1·07). Plasma NfL adjusted levels remained stable in non-progressors, but they showed an annual increase of 2·3 pg/ml (0·8–3·9) in the group of asymptomatic progressors, 3·3 pg/ml (1·6–4·9) in prodromal Alzheimer’s disease progressors, and 6·5 pg/ml (3·2–9·8 pg/ml) in participants with Alzheimer’s disease dementia. Plasma NfL levels have excellent diagnostic and prognostic performance for the diagnosis of symptomatic Alzheimer in Down syndrome. The longitudinal trajectory of plasma NfL enables its use as a theragnostic marker in clinical trials. AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Intitute on Aging, Wellcome Trust, Jerome Lejeune Foundation, Medical Research Council, NIHR, JPND, Alzheimer’s society, DFG, VERUM.