Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-1-23
|
| pubmed:abstractText |
Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Fibrillary Acidic Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
1078-8956
|
| pubmed:author |
pubmed-author:BenkovicSS,
pubmed-author:DuffKK,
pubmed-author:EckmanCC,
pubmed-author:GordonM NMN,
pubmed-author:HardyJJ,
pubmed-author:HolcombLL,
pubmed-author:HsiaoKK,
pubmed-author:JantzenPP,
pubmed-author:McGowanEE,
pubmed-author:MorganDD,
pubmed-author:MuellerRR,
pubmed-author:O'CampoKK,
pubmed-author:PradaC MCM,
pubmed-author:SaadII,
pubmed-author:SandersSS,
pubmed-author:WrightKK,
pubmed-author:YounkinSS,
pubmed-author:YuXX,
pubmed-author:ZehrCC
|
| pubmed:issnType |
Print
|
| pubmed:volume |
4
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
97-100
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9427614-Alzheimer Disease,
pubmed-meshheading:9427614-Amyloid beta-Protein Precursor,
pubmed-meshheading:9427614-Analysis of Variance,
pubmed-meshheading:9427614-Animals,
pubmed-meshheading:9427614-Brain,
pubmed-meshheading:9427614-Cerebral Cortex,
pubmed-meshheading:9427614-Crosses, Genetic,
pubmed-meshheading:9427614-Genotype,
pubmed-meshheading:9427614-Glial Fibrillary Acidic Protein,
pubmed-meshheading:9427614-Humans,
pubmed-meshheading:9427614-Membrane Proteins,
pubmed-meshheading:9427614-Mice,
pubmed-meshheading:9427614-Mice, Transgenic,
pubmed-meshheading:9427614-Motor Activity,
pubmed-meshheading:9427614-Posture,
pubmed-meshheading:9427614-Presenilin-1,
pubmed-meshheading:9427614-Psychomotor Performance,
pubmed-meshheading:9427614-Reflex,
pubmed-meshheading:9427614-Seizures
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes.
|
| pubmed:affiliation |
Department of Pharmacology, University of South Florida, Tampa 33612, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|