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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

TitleEpisodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalities
Authors
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
Citation
Neurobiology Of Disease, 2005, v. 18 n. 3, p. 602-617 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/81221
ISSN
2014 Impact Factor: 5.078
2014 SCImago Journal Rankings: 2.441
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSavonenko, Aen_HK
dc.contributor.authorXu, GMen_HK
dc.contributor.authorMelnikova, Ten_HK
dc.contributor.authorMorton, JLen_HK
dc.contributor.authorGonzales, Ven_HK
dc.contributor.authorWong, MPFen_HK
dc.contributor.authorPrice, DLen_HK
dc.contributor.authorTang, Fen_HK
dc.contributor.authorMarkowska, ALen_HK
dc.contributor.authorBorchelt, DRen_HK
dc.date.accessioned2010-09-06T08:15:12Z-
dc.date.available2010-09-06T08:15:12Z-
dc.date.issued2005en_HK
dc.identifier.citationNeurobiology Of Disease, 2005, v. 18 n. 3, p. 602-617en_HK
dc.identifier.issn0969-9961en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81221-
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.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynbdien_HK
dc.relation.ispartofNeurobiology of Diseaseen_HK
dc.subjectAgingen_HK
dc.subjectCholinergic systemen_HK
dc.subjectFactor analysisen_HK
dc.subjectRadial Water Mazeen_HK
dc.subjectSomatostatinen_HK
dc.titleEpisodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalitiesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0969-9961&volume=18&spage=602&epage=617&date=2005&atitle=Episodic-like+memory+deficits+in+the+APPswe/PS1dE9+mouse+model+of+Alzheimer’s+disease;+relationships+to+beta-amyloid+deposition+and+neurotransmitter+abnormalities.en_HK
dc.identifier.emailTang, F: ftang@hkucc.hku.hken_HK
dc.identifier.authorityTang, F=rp00327en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.nbd.2004.10.022en_HK
dc.identifier.pmid15755686en_HK
dc.identifier.scopuseid_2-s2.0-20044383377en_HK
dc.identifier.hkuros104271en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-20044383377&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue3en_HK
dc.identifier.spage602en_HK
dc.identifier.epage617en_HK
dc.identifier.isiWOS:000227820500019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSavonenko, A=6603804254en_HK
dc.identifier.scopusauthoridXu, GM=37030061200en_HK
dc.identifier.scopusauthoridMelnikova, T=14050419500en_HK
dc.identifier.scopusauthoridMorton, JL=8753051700en_HK
dc.identifier.scopusauthoridGonzales, V=6603939767en_HK
dc.identifier.scopusauthoridWong, MPF=36985740400en_HK
dc.identifier.scopusauthoridPrice, DL=35353856000en_HK
dc.identifier.scopusauthoridTang, F=7201979770en_HK
dc.identifier.scopusauthoridMarkowska, AL=7006391648en_HK
dc.identifier.scopusauthoridBorchelt, DR=7005319619en_HK

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