Linked Life Data

15115763

Source:http://linkedlifedata.com/resource/pubmed/id/15115763

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-5-24
pubmed:abstractText
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the impairment of cognitive functions and by beta amyloid (Abeta) plaques in the cerebral cortex and the hippocampus. Our objective was to determine genes that are critical for cellular changes in AD progression, with particular emphasis on changes early in disease progression. We investigated an established amyloid precursor protein (APP) transgenic mouse model (the Tg2576 mouse model) for gene expression profiles at three stages of disease progression: long before (2 months of age), immediately before (5 months) and after (18 months) the appearance of Abeta plaques. Using cDNA microarray techniques, we measured mRNA levels in 11 283 cDNA clones from the cerebral cortex of Tg2576 mice and age-matched wild-type (WT) mice at each of the three time points. This gene expression analysis revealed that the genes related to mitochondrial energy metabolism and apoptosis were up-regulated in 2-month-old Tg2576 mice and that the same genes were up-regulated at 5 and 18 months of age. These microarray results were confirmed using northern blot analysis. Results from in situ hybridization of mitochondrial genes-ATPase-6, heat-shock protein 86 and programmed cell death gene 8-suggest that the granule cells of the hippocampal dentate gyrus and the pyramidal neurons in the hippocampus and the cerebral cortex are up-regulated in Tg2576 mice compared with WT mice. Results from double-labeling in situ hybridization suggest that in Tg2576 mice only selective, over-expressed neurons with the mitochondrial gene ATPase-6 undergo oxidative damage. These results, therefore, suggest that mitochondrial energy metabolism is impaired by the expression of mutant APP and/or Abeta, and that the up-regulation of mitochondrial genes is a compensatory response. These findings have important implications for understanding the mechanism of Abeta toxicity in AD and for developing therapeutic strategies for AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1225-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15115763-Adenine, pubmed-meshheading:15115763-Alzheimer Disease, pubmed-meshheading:15115763-Amyloid beta-Protein Precursor, pubmed-meshheading:15115763-Animals, pubmed-meshheading:15115763-Apoptosis, pubmed-meshheading:15115763-Brain, pubmed-meshheading:15115763-Fluorescent Antibody Technique, pubmed-meshheading:15115763-Gene Expression Profiling, pubmed-meshheading:15115763-Heat-Shock Proteins, pubmed-meshheading:15115763-In Situ Hybridization, pubmed-meshheading:15115763-Mice, pubmed-meshheading:15115763-Mice, Transgenic, pubmed-meshheading:15115763-Mitochondria, pubmed-meshheading:15115763-Mitochondrial Proton-Translocating ATPases, pubmed-meshheading:15115763-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15115763-Oxidative Phosphorylation Coupling Factors, pubmed-meshheading:15115763-Oxidative Stress, pubmed-meshheading:15115763-RNA, Messenger, pubmed-meshheading:15115763-Reproducibility of Results
pubmed:year
2004
pubmed:articleTitle
Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease.
pubmed:affiliation
Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health and Science University, Beaverton, OR 97006, USA. reddyh@ohsu.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