A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition

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...

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Bibliographic Details
Published in:Neurobiology of aging 2009-07, Vol.30 (7), p.1078-1090
Main Authors: Flood, Dorothy G, Lin, Yin-Guo, Lang, Diane M, Trusko, Stephen P, Hirsch, James D, Savage, Mary J, Scott, Richard W, Howland, David S
Format: Article
Language:English
Subjects:
Age of Onset
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - physiopathology
Amyloid beta-Peptides - genetics
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Animals
Biomarkers
Brain - metabolism
Brain - pathology
Brain - physiopathology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Extracellular Fluid - metabolism
Gliosis - metabolism
Gliosis - pathology
Gliosis - physiopathology
Humans
Mice
Mice, Transgenic
Mutation - genetics
Neurofibrillary Tangles - genetics
Neurofibrillary Tangles - metabolism
Neurofibrillary Tangles - pathology
Phosphorylation
Plaque, Amyloid - genetics
Plaque, Amyloid - metabolism
Plaque, Amyloid - pathology
Presenilin-1 - genetics
Rats
Rats, Sprague-Dawley
Rats, Transgenic
tau Proteins - metabolism
Transgenes - genetics
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Summary: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.
ISSN:1558-1497