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

Abstract

Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (Aβ) have been produced, but development of an Aβ-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar Aβ 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. Aβ production in the double homozygous rats was sufficient for deposition by 17–18 months of age. The age of onset of Aβ 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 Aβ deposition by 7 months of age. Deposits appeared similar to those observed in the mouse models and displayed surrounding glial and phosphorylated tau reactivity. Aβ levels measured by ELISA were comparable to those reported in mouse models, suggesting that substantially greater amounts of soluble Aβ are not required in the rat to generate Aβ deposition.