Lipids

, Volume 49, Issue 5, pp 445–455

PCSK9 is Present in Human Cerebrospinal Fluid and is Maintained at Remarkably Constant Concentrations Throughout the Course of the Day

Authors

    • Lilly Research LaboratoriesEli Lilly and Company
  • Jason S. Troutt
    • Lilly Research LaboratoriesEli Lilly and Company
  • Robert J. Konrad
    • Lilly Research LaboratoriesEli Lilly and Company
Original Article

DOI: 10.1007/s11745-014-3895-6

Cite this article as:
Chen, Y.Q., Troutt, J.S. & Konrad, R.J. Lipids (2014) 49: 445. doi:10.1007/s11745-014-3895-6

Abstract

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum low density lipoprotein cholesterol levels. PCSK9 is secreted by the liver and binds the hepatic low density lipoprotein receptor, causing its subsequent degradation. PCSK9 has also been shown to regulate the levels of additional membrane-bound proteins in vitro, including very low-density lipoprotein receptor, apolipoprotein E receptor 2, and beta-site amyloid precursor protein-cleaving enzyme 1, which are highly expressed in central nervous system (CNS) and have been implicated in Alzheimer’s disease. Previous studies have demonstrated that human circulating PCSK9 displays a diurnal rhythm. Currently, little is known about PCSK9 levels in human cerebrospinal fluid (CSF). In the present study, we measured PCSK9 concentrations in both serum and CSF collected from healthy human subjects at multiple time points throughout the day. While PCSK9 in serum manifested a distinct diurnal pattern, CSF PCSK9 levels were remarkably constant throughout the course of the day and were also consistently lower than corresponding serum PCSK9 concentrations. Our results indicate that regulation of PCSK9 in human CSF may be different than for plasma PCSK9, suggesting that further study of the role of PCSK9 in the CNS is warranted.

Keywords

PCSK9LDL-cholesterolLDL receptorCerebrospinal fluidDiurnal variation

Abbreviations

AD

Alzheimer’s disease

ApoA1

Apolipoprotein A1

ApoB

Apolipoprotein B

ApoE

Apolipoprotein E

ApoER2

Apolipoprotein E receptor 2

BACE1

Beta-site amyloid precursor protein (APP)-cleaving enzyme

CHD

Coronary heart disease

CNS

Central nervous system

CSF

Cerebrospinal fluid

IDOL

Inducible degrader of LDLR

IP

Immunoprecipitation

LDL

Low density lipoprotein

LDL-C

Low density lipoprotein cholesterol

LDLR

Low density lipoprotein receptor

PCSK9

Proprotein convertase subtilisin kexin type 9

VLDLR

Very low-density lipoprotein receptor

WB

Western blotting

Copyright information

© AOCS 2014