SPION-Enhanced Magnetic Resonance Imaging of Alzheimer's Disease Plaques in A beta PP/PS-1 Transgenic Mouse Brain

In our program to develop non-invasive magnetic resonance imaging (MRI) methods for the diagnosis of Alzheimer's disease (AD), we have synthesized antibody-conjugated, superparamagnetic iron oxide nanoparticles (SPIONs) for use as an in vivo agent for MRI detection of amyloid-beta plaques in AD. Here we report studies in A beta PP/PS1 transgenic mice, which demonstrate the ability of novel anti-A beta PP conjugated SPIONs to penetrate the blood-brain barrier to act as a contrast agent for MR imaging of plaques. The conspicuity of the plaques increased from an average Z-score of 5.1 +/- 0.5 to 8.3 +/- 0.2 when the plaque contrast to noise ratio was compared in control AD mice with AD mice treated with SPIONs. The number of MRI-visible plaques per brain increased from 347 +/- 45 in the control AD mice, to 668 +/- 86 in the SPION treated mice. These results indicated that our SPION enhanced amyloid-beta detection method delivers an efficacious, non-invasive MRI detection method in transgenic mice.