在疾病前驱期，脑脊液总α-突触核蛋白检测对阿尔茨海默病与路易体痴呆的鉴别诊断价值。
Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage.
机构信息
Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, 67000, Strasbourg, France.
Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), University of Strasbourg, 67000, Strasbourg, France.
出版信息
Alzheimers Res Ther. 2020 Sep 29;12(1):120. doi: 10.1186/s13195-020-00684-5.
BACKGROUND
Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.
METHODS
All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured.
RESULTS
The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB.
CONCLUSIONS
The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer's biomarker does not improve the differential diagnosis between AD and DLB.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT01876459 (AlphaLewyMa).
背景
已有多项研究调查了在阿尔茨海默病（AD）和路易体痴呆（DLB）患者的脑脊液（CSF）中α-突触核蛋白检测的价值，以辅助这两种病理情况的鉴别诊断。然而，仅有极少数研究关注了处于轻度认知障碍（MCI）阶段的 AD 和 DLB 患者的该检测。
方法
所有患者均根据法国阿尔萨斯地区三级记忆诊所（CM2R）的医院临床研究方案，由经验丰富的临床医生团队纳入研究。共有 166 名患者纳入本研究：21 名对照受试者（CS）、51 名前驱期 DLB 患者（pro-DLB）、16 名痴呆期 DLB 患者（DLB-d）、33 名前驱期 AD 患者（pro-AD）、32 名痴呆期 AD 患者（AD-d）和 13 名混合病理患者（AD+DLB）。采用商业化的α-突触核蛋白酶联免疫吸附试验（ELISA）（AJ Roboscreen）评估 CSF 中总α-突触核蛋白水平。还测量了阿尔茨海默病生物标志物（t-Tau、P-Tau、Aβ42 和 Aβ40）。
结果
α-突触核蛋白检测在 AD 和 DLB 组之间显示出显著差异。AD 患者的总α-突触核蛋白水平明显高于 DLB 患者。然而，ROC 曲线显示 AD 和 DLB 之间具有中等的区分能力（AUC=0.78），且不提高阿尔茨海默病生物标志物组合（有或无α-突触核蛋白时 AUC=0.95）的区分能力。有趣的是，在 AD 和 DLB 中，水平似乎从前驱期开始就发生了改变。
结论
从前驱期开始，患者 CSF 中的总α-突触核蛋白水平发生改变。将总α-突触核蛋白添加到阿尔茨海默病生物标志物组合中并不能改善 AD 和 DLB 之间的鉴别诊断。
试验注册
ClinicalTrials.gov，NCT01876459（AlphaLewyMa）。
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