Detection of Amyloid Plaques Targeted by Bifunctional USPIO in Alzheimer’s Disease Transgenic Mice Using Magnetic Resonance Microimaging

Amyloid plaques are a key pathological hallmark of Alzheimer’s disease (AD). The detection of amyloid plaques in the brain is important for the diagnosis of AD, as well as for following potential amyloid targeting therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (mMRI) in AD transgenic mice, where we used mannitol to enhance blood brain barrier (BBB) permeability. In the present study, we used bifunctional ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Ab1-42 peptide to image amyloid plaque deposition in the mouse brain. We coupled the nanoparticles to polyethylene glycol (PEG) in order to improve BBB permeability. These USPIO-PEG-Ab1-42 nanoparticles were injected intravenously in AD model transgenic mice followed by initial in vivo and subsequent ex vivo mMRI. A 3D gradient multi-echo sequence was used for imaging with a 100 mm isotropic resolution. The amyloid plaques detected by T2*-weighted mMRI were confirmed with matched histological sections. The region of interest-based quantitative measurement of T2 * values obtained from the in vivo mMRI showed contrast injected AD Tg mice had significantly reduced T2 * values compared to wild-type mice. In addition, the ex vivo scans were examined with voxel-based analysis (VBA) using statistical parametric mapping (SPM) fo