Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease.

Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease.
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DOI:
10.1186/s13195-018-0404-9
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发表时间:
2018-07-28
期刊:
Alzheimer's research & therapy
影响因子:
--
通讯作者:
Zetterberg H
Zetterberg H
中科院分区:
其他
文献类型:
--
作者:
Lewczuk P;Ermann N;Andreasson U;Schultheis C;Podhorna J;Spitzer P;Maler JM;Kornhuber J;Blennow K;Zetterberg H

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越来越多的证据表明,神经丝轻链(NFL)的血浆浓度可能被认为是筛选阿尔茨海默病(AD)神经变性的血浆生物标志物。采用单分子阵列法(SIMA,Quanterix)检测99例AD患者轻度认知功能障碍(MCI-AD;n = 25)、早期痴呆期(ADD;n = 33)和非痴呆对照组(n = 41)的血浆NFL浓度,所有患者的临床诊断与4种核心脑脊液标志物(淀粉样蛋白β(Aβ)1-42、Aβ42/40、Tau和pTau181)的结果一致。在六种不同条件下的样品上测试了分析前存储程序对血浆中NFL的影响。与非痴呆对照组(22.0 ± 12.4npg/m l)相比,MCI-AD组未调整的血浆nfl浓度(38.1pg/m l,p < )显著升高(p < 0.005),ADD组进一步升高(49.1 ± 28.4npg/m L;p < 0.001)。NFL与年龄显著相关(ρ = 0.65,p < 0.001);在校正年龄后,AD组和对照组之间的NFL浓度差异仍然显著(p = 0.044)。以25.7 pg/mL为临界值,其无条件敏感性、特异性和准确性分别为0.84、0.78和0.82。所有患者的血浆神经营养因子与简易智力状态检查之间未经调整的相关性为中等但显著(r = −0.49,p < 0.001)。我们观察到血浆NFL和脑脊液生物标志物之间总体上有显著的相关性,但在诊断组中没有观察到这种相关性。这项研究证实,与非痴呆对照组相比,阿尔茨海默病患者的血浆NFL浓度增加。
A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer’s disease (AD). With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1–42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions. NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = −0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups. This study confirms increased concentrations of plasma NfL in patients with Alzheimer’s disease compared with nondemented controls.
存储时间和冻融周期对血清样品稳定性的影响。
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