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A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition.
Neurobiol Aging 2009; 30(7):1078-90NA

Abstract

Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (Abeta) have been produced, but development of an Abeta-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar Abeta deposition. Two lines of Sprague Dawley rats with transgenes expressing human amyloid precursor protein (APP) with the familial AD (FAD) mutations K670N/M671L and K670N/M671L/V717I were crossed. Abeta production in the double homozygous rats was sufficient for deposition by 17-18 months of age. The age of onset of Abeta deposition was reduced by crossing in a third rat line carrying a human presenilin-1 (PS-1) transgene with the FAD M146V mutation. The triple homozygous line had an onset of Abeta deposition by 7 months of age. Deposits appeared similar to those observed in the mouse models and displayed surrounding glial and phosphorylated tau reactivity. Abeta levels measured by ELISA were comparable to those reported in mouse models, suggesting that substantially greater amounts of soluble Abeta are not required in the rat to generate Abeta deposition.

Authors+Show Affiliations

Department of CNS Biology, Discovery Research, Cephalon, Inc., West Chester, PA 19380, USA. dflood@cephalon.comNo 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, Non-U.S. Gov't

Language

eng

PubMed ID

18053619

Citation

Flood, Dorothy G., et al. "A Transgenic Rat Model of Alzheimer's Disease With Extracellular Abeta Deposition." Neurobiology of Aging, vol. 30, no. 7, 2009, pp. 1078-90.
Flood DG, Lin YG, Lang DM, et al. A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition. Neurobiol Aging. 2009;30(7):1078-90.
Flood, D. G., Lin, Y. G., Lang, D. M., Trusko, S. P., Hirsch, J. D., Savage, M. J., ... Howland, D. S. (2009). A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition. Neurobiology of Aging, 30(7), pp. 1078-90.
Flood DG, et al. A Transgenic Rat Model of Alzheimer's Disease With Extracellular Abeta Deposition. Neurobiol Aging. 2009;30(7):1078-90. PubMed PMID: 18053619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition. AU - Flood,Dorothy G, AU - Lin,Yin-Guo, AU - Lang,Diane M, AU - Trusko,Stephen P, AU - Hirsch,James D, AU - Savage,Mary J, AU - Scott,Richard W, AU - Howland,David S, Y1 - 2007/11/28/ PY - 2007/06/05/received PY - 2007/09/24/revised PY - 2007/10/13/accepted PY - 2007/12/7/pubmed PY - 2009/8/22/medline PY - 2007/12/7/entrez SP - 1078 EP - 90 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 30 IS - 7 N2 - Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (Abeta) have been produced, but development of an Abeta-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar Abeta deposition. Two lines of Sprague Dawley rats with transgenes expressing human amyloid precursor protein (APP) with the familial AD (FAD) mutations K670N/M671L and K670N/M671L/V717I were crossed. Abeta production in the double homozygous rats was sufficient for deposition by 17-18 months of age. The age of onset of Abeta deposition was reduced by crossing in a third rat line carrying a human presenilin-1 (PS-1) transgene with the FAD M146V mutation. The triple homozygous line had an onset of Abeta deposition by 7 months of age. Deposits appeared similar to those observed in the mouse models and displayed surrounding glial and phosphorylated tau reactivity. Abeta levels measured by ELISA were comparable to those reported in mouse models, suggesting that substantially greater amounts of soluble Abeta are not required in the rat to generate Abeta deposition. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/18053619/A_transgenic_rat_model_of_Alzheimer's_disease_with_extracellular_Abeta_deposition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(07)00407-1 DB - PRIME DP - Unbound Medicine ER -