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Article: Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalities
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TitleEpisodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalities
 
AuthorsSavonenko, A4 4
Xu, GM4
Melnikova, T4
Morton, JL4
Gonzales, V4
Wong, MPF2
Price, DL4 4 4
Tang, F2
Markowska, AL1 3
Borchelt, DR4 4
 
KeywordsAging
Cholinergic system
Factor analysis
Radial Water Maze
Somatostatin
 
Issue Date2005
 
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynbdi
 
CitationNeurobiology Of Disease, 2005, v. 18 n. 3, p. 602-617 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.nbd.2004.10.022
 
AbstractTransgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Aβ42 production and provide a model of Alzheimer-type amyloidosis. Here, we examine cognition in 6- and 18-month old transgenic mice expressing APPswe and PS1dE9, alone and in combination. Spatial reference memory was assessed in a standard Morris Water Maze task followed by assessment of episodic-like memory in Repeated Reversal and Radial Water maze tasks. We then used factor analysis to relate changes in performance in these tasks with cholinergic markers, somatostatin levels, and amyloid burden. At 6 months of age, APPswe/PS1dE9 double-transgenic mice showed visible plaque deposition; however, all genotypes, including double-transgenic mice, were indistinguishable from nontransgenic animals in all cognitive measures. In the 18-month-old cohorts, amyloid burdens were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). APPswe/PS1dE9 mice performed all cognitive tasks less well than mice from all other genotypes. Factor and correlation analyses defined the strongest correlation as between deficits in episodic-like memory tasks and total Aβ loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Aβ associated with amyloid deposition can disrupt cognitive circuits when the cholinergic and somatostatinergic systems remain relatively intact; and that episodic-like memory seems to be more sensitive to the toxic effects of Aβ. © 2004 Elsevier Inc. All rights reserved.
 
ISSN0969-9961
2012 Impact Factor: 5.624
2012 SCImago Journal Rankings: 2.334
 
DOIhttp://dx.doi.org/10.1016/j.nbd.2004.10.022
 
ISI Accession Number IDWOS:000227820500019
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSavonenko, A
 
dc.contributor.authorXu, GM
 
dc.contributor.authorMelnikova, T
 
dc.contributor.authorMorton, JL
 
dc.contributor.authorGonzales, V
 
dc.contributor.authorWong, MPF
 
dc.contributor.authorPrice, DL
 
dc.contributor.authorTang, F
 
dc.contributor.authorMarkowska, AL
 
dc.contributor.authorBorchelt, DR
 
dc.date.accessioned2010-09-06T08:15:12Z
 
dc.date.available2010-09-06T08:15:12Z
 
dc.date.issued2005
 
dc.description.abstractTransgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Aβ42 production and provide a model of Alzheimer-type amyloidosis. Here, we examine cognition in 6- and 18-month old transgenic mice expressing APPswe and PS1dE9, alone and in combination. Spatial reference memory was assessed in a standard Morris Water Maze task followed by assessment of episodic-like memory in Repeated Reversal and Radial Water maze tasks. We then used factor analysis to relate changes in performance in these tasks with cholinergic markers, somatostatin levels, and amyloid burden. At 6 months of age, APPswe/PS1dE9 double-transgenic mice showed visible plaque deposition; however, all genotypes, including double-transgenic mice, were indistinguishable from nontransgenic animals in all cognitive measures. In the 18-month-old cohorts, amyloid burdens were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). APPswe/PS1dE9 mice performed all cognitive tasks less well than mice from all other genotypes. Factor and correlation analyses defined the strongest correlation as between deficits in episodic-like memory tasks and total Aβ loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Aβ associated with amyloid deposition can disrupt cognitive circuits when the cholinergic and somatostatinergic systems remain relatively intact; and that episodic-like memory seems to be more sensitive to the toxic effects of Aβ. © 2004 Elsevier Inc. All rights reserved.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationNeurobiology Of Disease, 2005, v. 18 n. 3, p. 602-617 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.nbd.2004.10.022
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.nbd.2004.10.022
 
dc.identifier.epage617
 
dc.identifier.hkuros104271
 
dc.identifier.isiWOS:000227820500019
 
dc.identifier.issn0969-9961
2012 Impact Factor: 5.624
2012 SCImago Journal Rankings: 2.334
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid15755686
 
dc.identifier.scopuseid_2-s2.0-20044383377
 
dc.identifier.spage602
 
dc.identifier.urihttp://hdl.handle.net/10722/81221
 
dc.identifier.volume18
 
dc.languageeng
 
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynbdi
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNeurobiology of Disease
 
dc.relation.referencesReferences in Scopus
 
dc.subjectAging
 
dc.subjectCholinergic system
 
dc.subjectFactor analysis
 
dc.subjectRadial Water Maze
 
dc.subjectSomatostatin
 
dc.titleEpisodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalities
 
dc.typeArticle
 
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Author Affiliations
  1. Johns Hopkins University
  2. The University of Hong Kong
  3. National Institute on Aging
  4. The Johns Hopkins School of Medicine