Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Alzheimer's disease is a learning and memory disorder pathologically characterized by the deposition of beta-amyloid plaques and loss of neurons and synapses in affected areas of the brain. Mutations in presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease (FAD), and are associated with accelerated plaque deposition. However, since the function of PS1 is pleiotropic, we reasoned that the FAD mutations may alter multiple PS1-mediated pathways, and the combination of which may account for the early onset nature of the disease phenotype. Using the PS1M146V knockin mice in which the M146V mutation was incorporated into the endogenous mouse PS1 gene, we report here that the FAD mutation results in impaired hippocampus-dependent associative learning, as measured by a contextual fear conditioning paradigm, at 3 months of age. This is correlated with reduced adult neurogenesis in the dentate gyrus. However, short-term and long-term synaptic plasticity in both area CA1 and dentate gyrus are not affected. Our results suggest that impaired adult neurogenesis may contribute to the memory deficit associated with FAD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:copyrightInfo
Copyright 2004 IBRO
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
305-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Presenilin 1 familial Alzheimer's disease mutation leads to defective associative learning and impaired adult neurogenesis.
pubmed:affiliation
Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, M320, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't