Structure and functions of human cerebrospinal fluid lipoproteins from individuals of different apoE genotypes

G. William Rebeck, Norma C. Alonzo, Oksana Berezovska, Steven D. Harr, Roger B. Knowles, John H. Growdon, Bradley T. Hyman, Armando J. Mendez

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Recent data have implicated apolipoprotein E (apoE) in neuritic outgrowth, synaptic stability, and Alzheimer's disease; these data led us to examine the normal role of apoE-containing lipoproteins in the central nervous system (CNS). We isolated lipoproteins from human cerobrospinal fluid (CSF) in order to examine their composition and potential functions. CSF particles were composed of approximately one-third protein, one-third phospholipid, and one-third cholesterol. ApoE3 formed homodimers and heterodimers with apoA-II, while apoE4, as expected, was monomeric. We addressed the function of CSF lipoproteins with assays of cholesterol efflux and cholesterol influx. CSF lipoproteins decreased intracellular levels of cholesterol in cholesterol-loaded fibroblasts, suggesting these particles can act to remove excess lipids from cells. CSF lipoproteins competed for 125 I-labeled LDL degradation by fibroblasts, suggesting they can also interact with the LDL receptor. Furthermore, CSF lipoproteins labeled with the fluorescent dye Dil were internalized by neuroglioma cells and primary neurons and astrocytes in culture. Together, these data support a model of CSF lipoproteins acting to remove lipids from degenerating cells and delivering lipids to cells for new membrane synthesis or storage.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalExperimental neurology
Volume149
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Cerebrospinal fluid
  • Lipoprotein
  • Neurodegeneration

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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