Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.
Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.
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DOI：
10.1212/wnl.0000000000004667
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发表时间：
2017-11-21
期刊：
影响因子：
9.9
通讯作者：
Fox NC
中科院分区：
文献类型：
--
作者：
Weston PSJ;Poole T;Ryan NS;Nair A;Liang Y;Macpherson K;Druyeh R;Malone IB;Ahsan RL;Pemberton H;Klimova J;Mead S;Blennow K;Rossor MN;Schott JM;Zetterberg H;Fox NC
研究家族性阿尔茨海默病（FAD）患者症状发作前后血清神经丝蛋白（NfL）浓度是否升高，以及是否与疾病分期和严重程度相关。我们从PSEN 1或APP突变家族中招募了48名个体进行横断面研究：18名有症状的阿尔茨海默病（AD），30名无症状但携带突变的风险为50%。使用单分子阵列（Simoa）平台上的超灵敏免疫测定来测量血清NfL。进行认知测试和MRI; 33名参与者进行了系列MRI，以计算萎缩率。基因检测确定了突变状态。采用广义最小二乘回归模型比较症状性突变携带者、症状前携带者和非携带者的血清NfL，调整年龄和性别。斯皮尔曼系数评估了血清NfL与（1）至症状发作（EYO）的估计年数、（2）认知测量和（3）萎缩的MRI测量之间的相关性。19名无症状的参与者是突变携带者（平均EYO −9.6）; 11名是非携带者。与非携带者相比，有症状（p < 0.0001）和症状前突变携带者（p = 0.007）的血清NfL浓度更高。在所有突变携带者中，血清NfL与EYO（ρ = 0.81，p < 0.0001）和多种认知和成像测量，包括简易精神状态检查（ρ = −0.62，p = 0.0001），临床痴呆评定量表方框总和（ρ = 0.79，p < 0.0001）、基线脑体积（ρ =-0.62，p = 0.0002）和全脑萎缩率（ρ = 0.53，p = 0.01）。FAD患者的血清NfL浓度在症状发作前升高，并与疾病分期和严重程度相关。因此，血清NfL可能是早期AD相关神经退行性变的可行生物标志物。
To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Nineteen of the asymptomatic participants were mutation carriers (mean EYO −9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = −0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = −0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration.