Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Alzheimers Res Ther. 2018 Nov 3;10(1):113. doi: 10.1186/s13195-018-0439-y.
Biomarkers that can track disease onset and progression in autosomal dominant Alzheimer's disease (ADAD) are needed. We investigate whether serum neurofilament light (NfL) concentration is associated with clinical and cerebrospinal fluid (CSF) markers in ADAD. We also evaluate serum NfL differences between clinical groups.
Serum NfL was measured cross-sectionally in 60 individuals from ADAD families using an ultrasensitive immunoassay on the Single molecule array (Simoa) platform and longitudinally in an exploratory study in a subset of six mutation carriers. Spearman coefficients assessed associations between serum NfL and relevant measures. Differences between groups were evaluated by Kruskal-Wallis and Mann-Whitney U tests.
Forty-two participants were mutation carriers: 22 symptomatic (SMC) and 20 asymptomatic (AMC). Eighteen subjects were non-carriers and cognitively normal (controls (CTR)). Serum NfL correlated with the estimated years from symptoms onset across mutation carriers (rho = 0.75, p < 0.001). In mutation carriers, serum NfL also showed strong correlation with clinical (rho = 0.70, p < 0.001) and cognitive (rho = -0.77, p < 0.001) measures and CSF NfL, total tau and phosphorylated tau levels (rho = 0.72, 0.71, and 0.71, respectively, all p < 0.001). Serum NfL concentration was higher in SMC than in AMC and CTR.
Serum NfL might be a feasible non-invasive biomarker to track disease onset and severity in ADAD.
需要能够追踪常染色体显性阿尔茨海默病（ADAD）发病和进展的生物标志物。我们研究了血清神经丝轻链（NfL）浓度与 ADAD 中的临床和脑脊液（CSF）标志物的相关性。我们还评估了临床组之间血清 NfL 的差异。
使用单分子阵列（Simoa）平台上的超敏免疫分析，在 60 名 ADAD 家族成员中进行了横断面血清 NfL 测量，并在 6 名突变携带者的探索性研究中进行了纵向测量。Spearman 系数评估了血清 NfL 与相关测量值之间的相关性。通过 Kruskal-Wallis 和 Mann-Whitney U 检验评估组间差异。
42 名参与者为突变携带者：22 名有症状（SMC）和 20 名无症状（AMC）。18 名受试者为非携带者且认知正常（对照组（CTR））。血清 NfL 与突变携带者从症状发作到估计的年数呈正相关（rho=0.75，p<0.001）。在突变携带者中，血清 NfL 与临床（rho=0.70，p<0.001）和认知（rho=-0.77，p<0.001）测量值以及 CSF NfL、总 tau 和磷酸化 tau 水平也呈强相关（rho=0.72、0.71 和 0.71，p 均<0.001）。SMC 的血清 NfL 浓度高于 AMC 和 CTR。
血清 NfL 可能是一种可行的非侵入性生物标志物，可用于追踪 ADAD 的发病和严重程度。
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