Département de Psychiatrie et de Médecine Addictologique, APHP GHU Nord, Site Lariboisière Fernand-Widal, Paris, France.
Inserm UMRS-1144 Optimisation thérapeutique en neuropsychopharmacologie, Université Paris Cité, Paris, France.
Addict Biol. 2022 Nov;27(6):e13232. doi: 10.1111/adb.13232.
In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.
在这项转化研究中，我们研究了血浆中的 tau 蛋白、神经丝轻链 (NfL)、胶质纤维酸性蛋白 (GFAP) 和泛素羧基末端水解酶 L1 (UCHL1)，这些都是神经损伤的既定生物标志物，可作为酒精戒断相关脑毒性的预测生物标志物。在临床研究中，我们比较了住院酒精戒断 (AC) 第 1 天的重度酒精使用障碍 (AUD) 患者 (N = 36) 与至少 3 个月戒断的重度 AUD 患者 (N = 16)。总体而言，患者中有 40 名男性 (76.9%)，年龄 49.8 ± 9.9 岁。使用 SIMOA 测量 tau、NfL、GFAP 和 UCHL1 水平，并使用调整年龄和性别的拟泊松回归模型进行分析。AC 组的 NfL 水平较高 (p = 0.013)。在 AC 组中，tau (p = 0.021) 和 UCHL1 (p = 0.021) 水平与体重每公斤的地西泮剂量呈正相关，tau (p = 0.045)、NfL (p = 4.9×10) 和 UCHL1 (p = 0.036) 水平在存在威尼克脑病迹象的情况下更高 (n = 9)。在临床前研究中，我们评估了酒精剥夺效应 (ADE) 程序中的 NfL 和 GFAP 水平 (N = 17) 和对照组 Wistar 大鼠 (N = 15)。此外，前瞻性评估了 ADE 大鼠：在 AC 后 24 小时 (T1) 和 3 周 (T2) (配对样本 Wilcoxon 和 Mann-Whitney 检验)。与对照组大鼠相比，ADE 模型在 T1 和 T2 时的 NfL 水平均较高 (p = 0.033 和 p = 1.3×10)，且 T2 时高于 T1 (p = 0.040)。血浆 tau、NfL 和 UCHL1 可能是酒精戒断期间大脑受损的潜在生物标志物。
