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

Published

Journal Article

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-beta. Under the same conditions, only a small fraction of A beta 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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • June 2005

Published In

Volume / Issue

  • 19 / 1-2

Start / End Page

  • 66 - 76

PubMed ID

  • 15837562

Pubmed Central ID

  • 15837562

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2004.11.005

Language

  • eng