Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid-high-density lipoprotein.
Alzheimer's disease
Amyloid β
Apolipoprotein E
Cerebrospinal fluid
Soluble LR11
Journal
Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
22
04
2018
revised:
06
11
2018
accepted:
14
11
2018
pubmed:
19
11
2018
medline:
19
3
2019
entrez:
19
11
2018
Statut:
ppublish
Résumé
LR11 is a member of the low-density lipoprotein (LDL) receptor family with high expression in neurons. Some cell surface LR11 is cleaved and secreted into the cerebrospinal fluid (CSF) as soluble LR11 (sLR11). Patients with Alzheimer's disease (AD), particularly apolipoprotein E4 carriers, have high CSF-sLR11 and low CSF-amyloid β (Aβ) concentrations. Therefore, we assessed whether sLR11 is bound to CSF-high-density lipoprotein (HDL) and whether sLR11 competes with Aβ in binding to apoE in CSF-HDL. We measured CSF-sLR11 concentrations (50 controls and 16 patients with AD) using enzyme immunoassay. sLR11 and apoE distribution in the CSF was evaluated using non-denaturing two-dimensional gel electrophoresis (N-2DGE). ApoE bound to sLR11 or Aβ was identified using co-immunoprecipitation assay. CSF-sLR11 concentrations were higher in patients with AD than controls (adjusted for sLR11 using phospholipid). N-2DGE analysis showed that sLR11 and Aβ comigrated with a large apoE-containing CSF-HDL. Moreover, fewer apoE was bound to Aβ when a higher amount of apoE was bound to sLR11 in patients with AD who presented with ε4/4. sLR11 binds to CSF-HDL and competes with Aβ in binding to apoE in CSF-HDL, indicating that sLR11 affects Aβ clearance via CSF-HDL.
Sections du résumé
BACKGROUND
BACKGROUND
LR11 is a member of the low-density lipoprotein (LDL) receptor family with high expression in neurons. Some cell surface LR11 is cleaved and secreted into the cerebrospinal fluid (CSF) as soluble LR11 (sLR11). Patients with Alzheimer's disease (AD), particularly apolipoprotein E4 carriers, have high CSF-sLR11 and low CSF-amyloid β (Aβ) concentrations. Therefore, we assessed whether sLR11 is bound to CSF-high-density lipoprotein (HDL) and whether sLR11 competes with Aβ in binding to apoE in CSF-HDL.
METHODS
METHODS
We measured CSF-sLR11 concentrations (50 controls and 16 patients with AD) using enzyme immunoassay. sLR11 and apoE distribution in the CSF was evaluated using non-denaturing two-dimensional gel electrophoresis (N-2DGE). ApoE bound to sLR11 or Aβ was identified using co-immunoprecipitation assay.
RESULTS
RESULTS
CSF-sLR11 concentrations were higher in patients with AD than controls (adjusted for sLR11 using phospholipid). N-2DGE analysis showed that sLR11 and Aβ comigrated with a large apoE-containing CSF-HDL. Moreover, fewer apoE was bound to Aβ when a higher amount of apoE was bound to sLR11 in patients with AD who presented with ε4/4.
CONCLUSION
CONCLUSIONS
sLR11 binds to CSF-HDL and competes with Aβ in binding to apoE in CSF-HDL, indicating that sLR11 affects Aβ clearance via CSF-HDL.
Identifiants
pubmed: 30448281
pii: S0009-8981(18)30605-3
doi: 10.1016/j.cca.2018.11.024
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoproteins E
0
LDL-Receptor Related Proteins
0
Lipoproteins
0
Membrane Transport Proteins
0
SORL1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
29-34Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.