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

Abstract

Background: 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.Methods: 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.Results: 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).Conclusions: 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.

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

“…The reason for this phenomenon may be that plasma PCSK9 levels are influenced by hormones such as estrogen [ 39 ]. Besides, we found that low PCSK9 levels were associated with the feature of smoking and drinking was inconsistent with other studies [ 40 , 41 ], which may need to investigate further in a large sample study.…”

Depression and cardiovascular risk—association among Beck Depression Inventory, PCSK9 levels and insulin resistance

“…In the context of CV prediction, PCSK9 concentrations, increased by insulin-resistance [ 18 ], are also associated with a raised susceptibility to MI, as assessed by genome association studies [ 19 ], although data from epidemiological studies are discordant [ 20 – 23 ]. The association between mood disorders and PCSK9 levels have received a significant contribution from a recent study on subjects affected by alcohol use disorder showing that PCSK9 cerebrospinal fluid levels are associated with the severity of behavioral disturbances [ 24 ].…”

Using genetic variants to evaluate the causal effect of cholesterol lowering on head and neck cancer risk: a Mendelian randomization study

“…The copyright holder for this this version posted October 7, 2020. ; https://doi.org/10.1101/2020. 10 disorder, including the interesting possibility of using anti-PSCK9 monoclonal antibodies for the treatment of alcoholic liver disease [63,64]. Given that alcohol is a well-known risk factor for HNSCC, this pleiotropy could have partially explained the effect seen in our study, however we proxied the inhibition of PCSK9 and so would have expected to see a protective effect of this gene in HNSCC cases who may have been heavy alcohol drinkers.…”