Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration

Casey Bassett, Larry L. Swift, Kathleen S. Montine, William R. Markesbery, Thomas J. Montine

Research output: Contribution to journalArticle

Abstract

Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration.

Original languageEnglish (US)
Pages (from-to)19-30
Number of pages12
JournalJournal of Alzheimer's Disease
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Apolipoproteins E
Lipoproteins
Cerebrospinal Fluid
Alzheimer Disease
Artificial Cells
Lipids
Neurons
Astrocytoma
Neuroblastoma
Alleles
Genotype

Keywords

  • Alzheimer's disease
  • Cerebrospinal fluid
  • DiI
  • Lipoproteins
  • Oxidation

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration. / Bassett, Casey; Swift, Larry L.; Montine, Kathleen S.; Markesbery, William R.; Montine, Thomas J.

In: Journal of Alzheimer's Disease, Vol. 4, No. 1, 01.01.2002, p. 19-30.

Research output: Contribution to journalArticle

Bassett, Casey ; Swift, Larry L. ; Montine, Kathleen S. ; Markesbery, William R. ; Montine, Thomas J. / Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration. In: Journal of Alzheimer's Disease. 2002 ; Vol. 4, No. 1. pp. 19-30.
@article{18f3fee7e4a14298b81f5de0b02fd3f8,
title = "Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration",
abstract = "Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration.",
keywords = "Alzheimer's disease, Cerebrospinal fluid, DiI, Lipoproteins, Oxidation",
author = "Casey Bassett and Swift, {Larry L.} and Montine, {Kathleen S.} and Markesbery, {William R.} and Montine, {Thomas J.}",
year = "2002",
month = "1",
day = "1",
doi = "10.3233/JAD-2002-4103",
language = "English (US)",
volume = "4",
pages = "19--30",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

TY - JOUR

T1 - Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration

AU - Bassett, Casey

AU - Swift, Larry L.

AU - Montine, Kathleen S.

AU - Markesbery, William R.

AU - Montine, Thomas J.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration.

AB - Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration.

KW - Alzheimer's disease

KW - Cerebrospinal fluid

KW - DiI

KW - Lipoproteins

KW - Oxidation

UR - http://www.scopus.com/inward/record.url?scp=0036129130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036129130&partnerID=8YFLogxK

U2 - 10.3233/JAD-2002-4103

DO - 10.3233/JAD-2002-4103

M3 - Article

C2 - 12214015

AN - SCOPUS:0036129130

VL - 4

SP - 19

EP - 30

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -