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

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‐as...

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Published in:Addiction biology 2022-11, Vol.27 (6), p.e13232-n/a
Main Authors: Clergue‐Duval, Virgile, Vrillon, Agathe, Jeanblanc, Jérôme, Questel, Frank, Azuar, Julien, Fouquet, Grégory, Mouton‐Liger, François, Rollet, Dorian, Hispard, Eric, Bouaziz‐Amar, Elodie, Bloch, Vanessa, Dereux, Alexandra, Cognat, Emmanuel, Marie‐Claire, Cynthia, Laplanche, Jean‐Louis, Bellivier, Frank, Paquet, Claire, Naassila, Mickael, Vorspan, Florence
Format: Article
Language:English
Subjects:
alcohol brain damage
alcohol use disorder
Alcoholism
Animals
Biomarkers
Brain
Cohort Studies
Glial Fibrillary Acidic Protein
Human health and pathology
Life Sciences
neurofilament light chain
Neurofilament Proteins
Pilot Projects
Rats
Rats, Wistar
Substance Withdrawal Syndrome
tau protein
Ubiquitin Thiolesterase
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Summary: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 × 10−3) 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 × 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. This translational study shows that plasma NfL, tau protein and UCHL1 are promising potential biomarkers of alcohol withdrawal‐associated brain suffering in severe alcohol use disorder. This results open an avenue for a brand new research field involving the identification of plasmatic biomarkers of brain damage associated with alcohol withdrawal, their validation as diagnostic tools for addiction as a brain disease and the search for peripheral therapeutic targets for the development of innovative drugs.
ISSN:1355-6215
1369-1600
DOI:10.1111/adb.13232