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 language | English |
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Pages (from-to) | 66-76 |
Number of pages | 11 |
Journal | Neurobiology of Disease |
Volume | 19 |
Issue number | 1-2 |
DOIs | |
State | Published - 2005 |
Keywords
- Amyloid
- Apolipoprotein E
- Astrocyte
- Aβ
- High-density lipoprotein
- Immortalization
- Knock-in mice