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A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment.
Neurobiol Dis 2008; 31(1):46-57ND

Abstract

In the last decade, multiple lines of transgenic APP overexpressing mice have been created that recapitulate certain aspects of Alzheimer's disease (AD). However, none of the previously reported transgenic APP overexpressing rat models developed AD-like beta-amyloid (Abeta) deposits, or age-related learning and memory deficits. In the present study, we have characterized a transgenic rat model overexpressing transgenes with three, familial AD mutations (two in APP and one in PS1) that were developed by Flood et al. [Flood, D.G., et al., Abeta deposition in a transgenic rat model of Alzheimer's disease. Society for Neuroscience 2003, Washington, DC, 2003]. From the age of 9 months, these rats develop Abeta deposits in both diffuse and compact forms, with the latter being closely associated with activated microglia and reactive astrocytes. Impaired long-term potentiation (LTP) was revealed by electrophysiological recordings performed on hippocampal slices from rats at 7 months of age, which is 2 months before the appearance of amyloid plaques. The deficit in LTP was accompanied by impaired spatial learning and memory in the Morris water maze, which became more pronounced in transgenic rats of 13 months of age. For Tg rats of both ages, there was a trend for cognitive impairment to correlate with total Abeta42 levels in the hippocampus. The rat model therefore recapitulates AD-like amyloid pathology and cognitive impairment. The advantage of the rat model over the available mouse models is that rats provide better opportunities for advanced studies, such as serial CSF sampling, electrophysiology, neuroimaging, cell-based transplant manipulations, and complex behavioral testing.

Authors+Show Affiliations

Department of Pathology, Taub Institute for Research on Alzheimer's Disease, Columbia University, Black Building #5-513, 650 West 168th Street, New York, NY 10032, USA.No 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18504134

Citation

Liu, Li, et al. "A Transgenic Rat That Develops Alzheimer's Disease-like Amyloid Pathology, Deficits in Synaptic Plasticity and Cognitive Impairment." Neurobiology of Disease, vol. 31, no. 1, 2008, pp. 46-57.
Liu L, Orozco IJ, Planel E, et al. A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurobiol Dis. 2008;31(1):46-57.
Liu, L., Orozco, I. J., Planel, E., Wen, Y., Bretteville, A., Krishnamurthy, P., ... Duff, K. (2008). A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurobiology of Disease, 31(1), pp. 46-57. doi:10.1016/j.nbd.2008.03.005.
Liu L, et al. A Transgenic Rat That Develops Alzheimer's Disease-like Amyloid Pathology, Deficits in Synaptic Plasticity and Cognitive Impairment. Neurobiol Dis. 2008;31(1):46-57. PubMed PMID: 18504134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. AU - Liu,Li, AU - Orozco,Ian J, AU - Planel,Emmanuel, AU - Wen,Yi, AU - Bretteville,Alexis, AU - Krishnamurthy,Pavan, AU - Wang,Lili, AU - Herman,Mathieu, AU - Figueroa,Helen, AU - Yu,W Haung, AU - Arancio,Ottavio, AU - Duff,Karen, Y1 - 2008/04/07/ PY - 2008/01/04/received PY - 2008/03/07/revised PY - 2008/03/15/accepted PY - 2008/5/28/pubmed PY - 2008/7/30/medline PY - 2008/5/28/entrez SP - 46 EP - 57 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 31 IS - 1 N2 - In the last decade, multiple lines of transgenic APP overexpressing mice have been created that recapitulate certain aspects of Alzheimer's disease (AD). However, none of the previously reported transgenic APP overexpressing rat models developed AD-like beta-amyloid (Abeta) deposits, or age-related learning and memory deficits. In the present study, we have characterized a transgenic rat model overexpressing transgenes with three, familial AD mutations (two in APP and one in PS1) that were developed by Flood et al. [Flood, D.G., et al., Abeta deposition in a transgenic rat model of Alzheimer's disease. Society for Neuroscience 2003, Washington, DC, 2003]. From the age of 9 months, these rats develop Abeta deposits in both diffuse and compact forms, with the latter being closely associated with activated microglia and reactive astrocytes. Impaired long-term potentiation (LTP) was revealed by electrophysiological recordings performed on hippocampal slices from rats at 7 months of age, which is 2 months before the appearance of amyloid plaques. The deficit in LTP was accompanied by impaired spatial learning and memory in the Morris water maze, which became more pronounced in transgenic rats of 13 months of age. For Tg rats of both ages, there was a trend for cognitive impairment to correlate with total Abeta42 levels in the hippocampus. The rat model therefore recapitulates AD-like amyloid pathology and cognitive impairment. The advantage of the rat model over the available mouse models is that rats provide better opportunities for advanced studies, such as serial CSF sampling, electrophysiology, neuroimaging, cell-based transplant manipulations, and complex behavioral testing. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/18504134/A_transgenic_rat_that_develops_Alzheimer's_disease_like_amyloid_pathology_deficits_in_synaptic_plasticity_and_cognitive_impairment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(08)00052-1 DB - PRIME DP - Unbound Medicine ER -