PCSK9 is Increased in Cerebrospinal Fluid of Individuals With Alcohol Use Disorder.

Abstract

Recent studies have shown that alcohol use affects the regulation and expression of proprotein convertase subtilisin/kexin 9 (PCSK9). While a major role of PCSK9 in hepatic function and lipid regulation has been clearly established, other pleiotropic effects remain poorly understood. Existing research suggests a positive association between PCSK9 expression in the brain and psychopathology, with increased levels of PCSK9 in the cerebrospinal fluid (CSF) of individuals with dementia and epigenetic modifications of PCSK9 associated with alcohol use disorder (AUD). In this study, we hypothesized that chronic alcohol use would increase PCSK9 expression in CSF. PCSK9 levels in CSF were measured in individuals with AUD (n=42) admitted to an inpatient rehabilitation program and controls (n=25). CSF samples in AUD were assessed at 2 time points, at day 5 and day 21 after admission. Furthermore, plasma samples were collected and measured from the individuals with AUD. PCSK9 in CSF was significantly increased in the AUD group at day 5 and day 21 compared to the controls (p<0.0001). Plasma PCSK9 levels were correlated positively with CSF PCSK9 levels in AUD (p=0.0493). Our data suggest that PCSK9 is elevated in the CSF of individuals with AUD, which may indicate a potential role of PCSK9 in AUD. Additional studies are necessary to further elucidate the functions of PCSK9 in the brain.