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Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities.
Neurobiol Dis 2005; 18(3):602-17ND

Abstract

Transgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Abeta42 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 Abeta loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Abeta 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 Abeta.

Authors+Show Affiliations

Department of Pathology, Johns Hopkins School of Medicine, Ross Building, Room 558, 720 Rutland Avenue, Baltimore, MD 21205, USA. asavone1@jhmi.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15755686

Citation

Savonenko, Alena, et al. "Episodic-like Memory Deficits in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease: Relationships to Beta-amyloid Deposition and Neurotransmitter Abnormalities." Neurobiology of Disease, vol. 18, no. 3, 2005, pp. 602-17.
Savonenko A, Xu GM, Melnikova T, et al. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis. 2005;18(3):602-17.
Savonenko, A., Xu, G. M., Melnikova, T., Morton, J. L., Gonzales, V., Wong, M. P., ... Borchelt, D. R. (2005). Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiology of Disease, 18(3), pp. 602-17.
Savonenko A, et al. Episodic-like Memory Deficits in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease: Relationships to Beta-amyloid Deposition and Neurotransmitter Abnormalities. Neurobiol Dis. 2005;18(3):602-17. PubMed PMID: 15755686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. AU - Savonenko,Alena, AU - Xu,Guilian M, AU - Melnikova,Tatiana, AU - Morton,Johanna L, AU - Gonzales,Victoria, AU - Wong,Molly P F, AU - Price,Donald L, AU - Tang,Fai, AU - Markowska,Alicja L, AU - Borchelt,David R, PY - 2003/12/03/received PY - 2004/10/18/revised PY - 2004/10/21/accepted PY - 2005/3/10/pubmed PY - 2005/5/18/medline PY - 2005/3/10/entrez SP - 602 EP - 17 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 18 IS - 3 N2 - Transgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Abeta42 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 Abeta loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Abeta 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 Abeta. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15755686/Episodic_like_memory_deficits_in_the_APPswe/PS1dE9_mouse_model_of_Alzheimer's_disease:_relationships_to_beta_amyloid_deposition_and_neurotransmitter_abnormalities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(04)00266-9 DB - PRIME DP - Unbound Medicine ER -