Gadolinium-staining reveals amyloid plaques in the brain of Alzheimer's transgenic mice

Detection of amyloidplaques in the brain by in vivo neuroimaging is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD) and evaluation of therapeutic efficacy. Here we describe a new method to detect amyloidplaques by in vivo magnetic resonance imaging (MRI) based on the intracerebroventricular injectionof a nontargeted gadolinium (Gd)-based contrast agent, which rapidly diffuses throughout the brain and increases the signal and contrast of magnetic resonance (MR) images by shortening the T1 relaxation time. This gain in image sensitivity after in vitro and in vivo Gd staining significantly improves the detection and resolution of individual amyloidplaques in the cortex and hippocampus of AD transgenic mice. The improved image resolutionis sensitive enough to demonstrate an age-dependent increase of amyloidplaque load and a good correlation between the amyloidload measured by MRI and histology. These results provide the first demonstration that nontargeted Gd staining can enhance the detection of amyloidplaques to follow the progression of AD and to evaluate the activity of amyloid-lowering therapeutic strategies in longitudinal studies.