Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β

Masayuki Morikawa, John D. Fryer, Patrick M. Sullivan, Erin A. Christopher, Suzanne E. Wahrle, Ronald B. DeMattos, Mark A. O'Dell, Anne M. Fagan, Hilal A. Lashuel, Thomas Walz, Kiyofumi Asai, David M. Holtzman

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice. APOE2, APOE3, and APOE4 expressing cell lines were established that secrete apoE in HDL-like particles at similar levels, cholesterol composition, and size as those produced by primary astrocytes. In physiological buffers, astrocyte-secreted apoE3 and E4 associated equally well with amyloid-β. Under the same conditions, only a small fraction of Aβ formed sodium dodecyl sulfate (SDS)-stable complexes with apoE (E3 > E4). These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS.

Original languageEnglish
Pages (from-to)66-76
Number of pages11
JournalNeurobiology of Disease
Volume19
Issue number1-2
DOIs
Publication statusPublished - 1 Jun 2005
Externally publishedYes

Fingerprint

Apolipoproteins E
Amyloid
Astrocytes
Protein Isoforms
Apolipoprotein E3
Central Nervous System
Cell Line
HDL Lipoproteins
Sodium Dodecyl Sulfate
Alzheimer Disease
Buffers
Cholesterol
Genotype

Keywords

  • Amyloid
  • Apolipoprotein E
  • Astrocyte
  • High-density lipoprotein
  • Immortalization
  • Knock-in mice

ASJC Scopus subject areas

  • Neurology

Cite this

Morikawa, M., Fryer, J. D., Sullivan, P. M., Christopher, E. A., Wahrle, S. E., DeMattos, R. B., ... Holtzman, D. M. (2005). Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β. Neurobiology of Disease, 19(1-2), 66-76. https://doi.org/10.1016/j.nbd.2004.11.005

Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β. / Morikawa, Masayuki; Fryer, John D.; Sullivan, Patrick M.; Christopher, Erin A.; Wahrle, Suzanne E.; DeMattos, Ronald B.; O'Dell, Mark A.; Fagan, Anne M.; Lashuel, Hilal A.; Walz, Thomas; Asai, Kiyofumi; Holtzman, David M.

In: Neurobiology of Disease, Vol. 19, No. 1-2, 01.06.2005, p. 66-76.

Research output: Contribution to journalArticle

Morikawa, M, Fryer, JD, Sullivan, PM, Christopher, EA, Wahrle, SE, DeMattos, RB, O'Dell, MA, Fagan, AM, Lashuel, HA, Walz, T, Asai, K & Holtzman, DM 2005, 'Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β', Neurobiology of Disease, vol. 19, no. 1-2, pp. 66-76. https://doi.org/10.1016/j.nbd.2004.11.005
Morikawa, Masayuki ; Fryer, John D. ; Sullivan, Patrick M. ; Christopher, Erin A. ; Wahrle, Suzanne E. ; DeMattos, Ronald B. ; O'Dell, Mark A. ; Fagan, Anne M. ; Lashuel, Hilal A. ; Walz, Thomas ; Asai, Kiyofumi ; Holtzman, David M. / Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β. In: Neurobiology of Disease. 2005 ; Vol. 19, No. 1-2. pp. 66-76.
@article{8617c3ecf2224dd4b6cad0753932c470,
title = "Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β",
abstract = "The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice. APOE2, APOE3, and APOE4 expressing cell lines were established that secrete apoE in HDL-like particles at similar levels, cholesterol composition, and size as those produced by primary astrocytes. In physiological buffers, astrocyte-secreted apoE3 and E4 associated equally well with amyloid-β. Under the same conditions, only a small fraction of Aβ formed sodium dodecyl sulfate (SDS)-stable complexes with apoE (E3 > E4). These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS.",
keywords = "Aβ, Amyloid, Apolipoprotein E, Astrocyte, High-density lipoprotein, Immortalization, Knock-in mice",
author = "Masayuki Morikawa and Fryer, {John D.} and Sullivan, {Patrick M.} and Christopher, {Erin A.} and Wahrle, {Suzanne E.} and DeMattos, {Ronald B.} and O'Dell, {Mark A.} and Fagan, {Anne M.} and Lashuel, {Hilal A.} and Thomas Walz and Kiyofumi Asai and Holtzman, {David M.}",
year = "2005",
month = "6",
day = "1",
doi = "10.1016/j.nbd.2004.11.005",
language = "English",
volume = "19",
pages = "66--76",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "1-2",

}

TY - JOUR

T1 - Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β

AU - Morikawa, Masayuki

AU - Fryer, John D.

AU - Sullivan, Patrick M.

AU - Christopher, Erin A.

AU - Wahrle, Suzanne E.

AU - DeMattos, Ronald B.

AU - O'Dell, Mark A.

AU - Fagan, Anne M.

AU - Lashuel, Hilal A.

AU - Walz, Thomas

AU - Asai, Kiyofumi

AU - Holtzman, David M.

PY - 2005/6/1

Y1 - 2005/6/1

N2 - The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice. APOE2, APOE3, and APOE4 expressing cell lines were established that secrete apoE in HDL-like particles at similar levels, cholesterol composition, and size as those produced by primary astrocytes. In physiological buffers, astrocyte-secreted apoE3 and E4 associated equally well with amyloid-β. Under the same conditions, only a small fraction of Aβ formed sodium dodecyl sulfate (SDS)-stable complexes with apoE (E3 > E4). These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS.

AB - The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice. APOE2, APOE3, and APOE4 expressing cell lines were established that secrete apoE in HDL-like particles at similar levels, cholesterol composition, and size as those produced by primary astrocytes. In physiological buffers, astrocyte-secreted apoE3 and E4 associated equally well with amyloid-β. Under the same conditions, only a small fraction of Aβ formed sodium dodecyl sulfate (SDS)-stable complexes with apoE (E3 > E4). These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS.

KW - Aβ

KW - Amyloid

KW - Apolipoprotein E

KW - Astrocyte

KW - High-density lipoprotein

KW - Immortalization

KW - Knock-in mice

UR - http://www.scopus.com/inward/record.url?scp=20244388997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244388997&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2004.11.005

DO - 10.1016/j.nbd.2004.11.005

M3 - Article

C2 - 15837562

AN - SCOPUS:20244388997

VL - 19

SP - 66

EP - 76

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1-2

ER -