Linked Life Data

15584908

Source:http://linkedlifedata.com/resource/pubmed/id/15584908

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-12-8
pubmed:abstractText
Inheritance of the apolipoprotein (APO) E gene epsilon4 or epsilon2 allele alters the risk of developing Alzheimer disease (AD), while increased alpha-tocopherol (AT) intake appears to lower the risk of AD. As APOE is a major apolipoprotein in the CNS and AT in vivo is transported in lipoproteins, we tested the hypothesis that CNS lipoproteins, as modeled by relevant concentrations of high density lipoprotein (HDL), and AT would interact to suppress neurotoxicity in a cell culture model of amyloid beta (Abeta)- related toxicity. These cells conditionally express C99-derived peptides, proposed to be a key step in AD pathogenesis; this expression is closely associated with subsequent cell death. We found that physiologic concentrations of lipoproteins present in the CNS protected from C99-associated toxicity and provided evidence for two mechanisms of protection. The first was AT-independent, APOE isoform-dependent, and most potent for the APOE2 isoform. The second was a synergistic protection afforded by a combination of APOAI, or less so APOE, and AT. These data provide a novel explanation for the apparent AD-protective effect of inheriting an epsilon2 APOE allele, and suggest that optimizing AT enrichment of CNS lipoproteins or devising APOAI mimetics may augment AT efficacy in treating AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1312-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment-associated cytotoxicity.
pubmed:affiliation
Department of Pathology, University of Washington, Seattle, Washington 98104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't