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 language | English |
|---|---|
| Pages (from-to) | 175-182 |
| Number of pages | 8 |
| Journal | Experimental Neurology |
| Volume | 149 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 1998 |
| Externally published | Yes |
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Keywords
- Alzheimer's disease
- Apolipoprotein E
- Cerebrospinal fluid
- Lipoprotein
- Neurodegeneration
ASJC Scopus subject areas
- Neurology
- Neuroscience(all)
Cite this
Structure and functions of human cerebrospinal fluid lipoproteins from individuals of different apoE genotypes. / Rebeck, G. William; Alonzo, Norma C.; Berezovska, Oksana; Harr, Steven D.; Knowles, Roger B.; Growdon, John H.; Hyman, Bradley T.; Mendez, Armando J.
In: Experimental Neurology, Vol. 149, No. 1, 01.01.1998, p. 175-182.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structure and functions of human cerebrospinal fluid lipoproteins from individuals of different apoE genotypes
AU - Rebeck, G. William
AU - Alonzo, Norma C.
AU - Berezovska, Oksana
AU - Harr, Steven D.
AU - Knowles, Roger B.
AU - Growdon, John H.
AU - Hyman, Bradley T.
AU - Mendez, Armando J
PY - 1998/1/1
Y1 - 1998/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - Cerebrospinal fluid
KW - Lipoprotein
KW - Neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=0031914130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031914130&partnerID=8YFLogxK
U2 - 10.1006/exnr.1997.6710
DO - 10.1006/exnr.1997.6710
M3 - Article
C2 - 9454626
AN - SCOPUS:0031914130
VL - 149
SP - 175
EP - 182
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -