Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-7-11
pubmed:abstractText
The apolipoprotein E (apoE) epsilon 4 allele (apoE4) is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A role for apoE in regeneration of synaptic circuitry after neural injury has been shown in several in vitro studies in which apoE3 supports neuronal sprouting better than apoE4. We evaluated sprouting in an in vitro mouse organotypic hippocampal slice culture system derived from transgenic mice expressing apoE3 or apoE4, in which apoE-dependent granule cell mossy fiber sprouting in the presence of apoE4 is only 51% of the level of apoE3. Sprouting supported by apoE4 had a dose response opposite that by supported by apoE3: although increasing E3 expression increased sprouting, increasing E4 expression decreased sprouting, suggesting that the defect in E4 in supporting neuronal sprouting is a gain-of-negative activity. These results may have important pharmacogenomic implications for AD therapies that modulate apoE expression levels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
331-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12111863-Alzheimer Disease, pubmed-meshheading:12111863-Animals, pubmed-meshheading:12111863-Animals, Newborn, pubmed-meshheading:12111863-Apolipoprotein E3, pubmed-meshheading:12111863-Apolipoprotein E4, pubmed-meshheading:12111863-Apolipoproteins E, pubmed-meshheading:12111863-Cell Differentiation, pubmed-meshheading:12111863-Female, pubmed-meshheading:12111863-Gene Expression Regulation, Developmental, pubmed-meshheading:12111863-Genetic Predisposition to Disease, pubmed-meshheading:12111863-Growth Cones, pubmed-meshheading:12111863-Heterozygote, pubmed-meshheading:12111863-Humans, pubmed-meshheading:12111863-Male, pubmed-meshheading:12111863-Mice, pubmed-meshheading:12111863-Mice, Inbred C57BL, pubmed-meshheading:12111863-Mice, Transgenic, pubmed-meshheading:12111863-Mossy Fibers, Hippocampal, pubmed-meshheading:12111863-Neuronal Plasticity, pubmed-meshheading:12111863-Phenotype, pubmed-meshheading:12111863-Protein Isoforms, pubmed-meshheading:12111863-Up-Regulation
pubmed:year
2002
pubmed:articleTitle
Defective neuronal sprouting by human apolipoprotein E4 is a gain-of-negative function.
pubmed:affiliation
Veterans Administration Greater Los Angeles Healthcare System and Department of Medicine, University of California, Los Angeles, Sepulveda, California 91343, USA. bteter@ucla.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't