Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study

被引:6
|
作者
Clergue-Duval, Virgile [1 ,2 ,3 ,4 ,5 ]
Vrillon, Agathe [2 ,3 ,4 ,6 ]
Jeanblanc, Jerome [7 ,8 ]
Questel, Frank [1 ,2 ,3 ,5 ]
Azuar, Julien [1 ,2 ,3 ,5 ]
Fouquet, Gregory [7 ,8 ]
Mouton-Liger, Francois [2 ,3 ,4 ,6 ]
Rollet, Dorian [1 ,3 ,5 ]
Hispard, Eric [1 ,3 ,5 ]
Bouaziz-Amar, Elodie [2 ,3 ,9 ,10 ]
Bloch, Vanessa [2 ,3 ,10 ,11 ]
Dereux, Alexandra [1 ,2 ,3 ,5 ]
Cognat, Emmanuel [2 ,3 ,4 ,6 ]
Marie-Claire, Cynthia [2 ,3 ]
Laplanche, Jean-Louis [2 ,3 ,9 ,10 ]
Bellivier, Frank [1 ,2 ,3 ,4 ]
Paquet, Claire [2 ,3 ,4 ,6 ]
Naassila, Mickael [7 ,8 ,12 ]
Vorspan, Florence [1 ,2 ,3 ,4 ]
机构
[1] Site Lariboisiere Fernand Widal, AP HP GHU Nord, Dept Psychiat & Med Addictol, Paris, France
[2] Univ Paris Cite, INSERM, Optimisat Therapeut Neuropsychopharmacol, UMRS 1144, Paris, France
[3] FHU Network Res Subst Use Disorders NOR SUD, Paris, France
[4] Univ Paris Cite, UFR Med, Paris, France
[5] Resalcog Reseau Prise Charge Troubles Cognitifs L, Paris, France
[6] Site Lariboisiere Fernand Widal, AP HP GHU Nord, Ctr Neurol Cognit, Paris, France
[7] Univ Picardie Jules Verne, Grp Rech Alcool & Pharmacodependances, UMRS 1247, INSERM, Amiens, France
[8] FHU Ameliorer Pronost Troubles Addictifs & Mentau, Amiens, France
[9] Site Lariboisiere Fernand Widal, AP HP GHU Nord, Dept Biochim & Biol Mol, Paris, France
[10] Univ Paris Cite, UFR Pharm, Paris, France
[11] Site Lariboisiere Fernand Widal, AP HP GHU Nord, Serv Pharm, Paris, France
[12] Univ Picardie Jules Verne, UFR Pharm, Amiens, France
关键词
alcohol brain damage; alcohol use disorder; biomarkers; neurofilament light chain; rats; tau protein; FIBRILLARY ACIDIC PROTEIN; ETHANOL-CONSUMPTION; DEFICIENCY; ASTROCYTES; HUMANS; CORTEX; MODEL;
D O I
10.1111/adb.13232
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 10(-3)) 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 x 10(-3)) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.
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页数:12
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