Longitudinal Study of Plasma NFL and GFAP as Biomarkers of Alcohol Withdrawal-Associated Brain Injury

Plasma neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), tau protein and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are candidate biomarkers of alcohol withdrawal (AW)-associated brain toxicity, as they are biomarkers of axonal, neuronal or glial injury. The aim of this study was to investigate the changes of these biomarkers during AW in patients with severe alcohol use disorder (AUD). Plasma NFL, GFAP, tau and UCHL1 levels were measured, with SIMOA, at three times: on Day 1 (T1), on Day 3 or 4 (T2) and on Day 13, 14 or 15 (T3) of AW. They were analysed with a linear mixed model adjusted for age, sex and body mass index. Changes in these levels according to AW symptom severity were evaluated. Twenty-four inpatients with severe AUD were included: 20 men (83.3%), aged 47.4 years [±11.3], with symptoms requiring a median equivalent-diazepam dose of 0.81 mg/kg at T1. A significant increase was observed for NFL level from T1 to T2 (β = 0.349, p = 0.035), but not for GFAP, tau or UCHL1 levels. In AW symptom severity analyses, a significant positive association was found with equivalent-diazepam dose required × T1-T2 time interaction factor for NFL (β = 0.161, p = 0.028) and for GFAP (β = 0.400, p = 9.9 × 10^-4). This longitudinal study provided preliminary indication that brain injury could occur within the first days of AW, especially in patients with severe pharmacological dependence. Plasma NFL and GFAP are promising biomarkers of AW-related brain pathology and should be investigated as biomarkers of therapeutic response to test innovative drug strategies for preventing this toxicity. Trial Registration: Clinical Trials: NCT05216705.