Impaired Eyeblink Conditioning and Decreased Hippocampal Volume in PDAPP V717F Mice

We examined heterozygous transgenic (Tg) mice that overexpress V717F amyloid precursor protein (APP) for delay eyeblink conditioning (EBC) and hippocampal volume with magnetic resonance imaging (MRI). Platelet-derived APP mice were significantly impaired on EBC relative to wild type (WT) litter-mate controls. T2-weighted spin echo images (62.5 × 125 × 500 μm) of the same mice were acquired under anesthesia using a 9.4T magnet. Tg mice had hippocampal to brain volume ratios that were significantly smaller than WT controls (31% smaller in the rostral dorsal hippocampus, 13–22% smaller among equal dorsal–ventral thirds of a caudal section). These results indicate that overexpression of APP or beta amyloid profoundly affects learning and memory and hippocampal volume. The results also indicate that eyeblink conditioning and quantitative MRI in mice may be useful assays to follow the progression of disease-related changes, and to test the effectiveness of potential therapeutics against Alzheimer's disease.