Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Alcohol Clin Exp Res. 2019 Jun;43(6):1163-1169. doi: 10.1111/acer.14039. Epub 2019 May 3.
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.
最近的研究表明，酒精使用会影响前蛋白转化酶枯草溶菌素/克胰蛋白酶 9（PCSK9）的调节和表达。虽然 PCSK9 在肝功能和脂质调节中的主要作用已得到明确证实，但其他多效性作用仍知之甚少。现有研究表明，脑内 PCSK9 表达与精神病理学之间存在正相关关系，痴呆患者脑脊液（CSF）中的 PCSK9 水平升高，与酒精使用障碍（AUD）相关的 PCSK9 表观遗传修饰。在这项研究中，我们假设慢性酒精使用会增加 CSF 中的 PCSK9 表达。
在接受住院康复治疗的 AUD 患者（n=42）和对照组（n=25）中测量 CSF 中的 PCSK9 水平。AUD 中的 CSF 样本在入院后第 5 天和第 21 天进行评估。此外，还从 AUD 患者中采集并测量了血浆样本。
与对照组相比，AUD 组在第 5 天和第 21 天 CSF 中的 PCSK9 显著增加（p<0.0001）。AUD 患者的血浆 PCSK9 水平与 CSF PCSK9 水平呈正相关（p=0.0493）。
我们的数据表明，AUD 患者的 CSF 中 PCSK9 升高，这可能表明 PCSK9 在 AUD 中起作用。需要进一步的研究来进一步阐明 PCSK9 在大脑中的功能。
