Amyloid plaques are one of the pathological hallmarks of
Alzheimer's disease (AD). The visualization of
amyloid plaques in the brain is important to monitor AD progression and to evaluate the efficacy of therapeutic interventions. Our group has developed several
contrast agents to detect
amyloid plaques in vivo using magnetic resonance microimaging (μMRI) in AD transgenic mice, where we used intra-carotid
mannitol to enhance blood-brain barrier (BBB) permeability. In the present study, we used
ultrasmall superparamagnetic iron oxide (
USPIO) nanoparticles, chemically coupled with Aβ1-42
peptide to detect
amyloid deposition along with
mannitol for in vivo μMRI by femoral
intravenous injection. A 3D gradient multi-echo sequence was used for imaging with a 100μm isotropic resolution. The
amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. Furthermore, two different quantitative analyses were used. The region of interest-based quantitative measurement of T2* values showed contrast-injected APP/PS1 mice had significantly reduced T2* values compared to wild-type mice. In addition, the scans were examined with voxel-based morphometry (VBM) using statistical parametric mapping (SPM) for comparison of contrast-injected AD transgenic and wild-type mice. The regional differences seen in VBM comparing USPIO-Aβ1-42 injected APP/PS1 and wild-type mice correlated with the
amyloid plaque distribution histologically, contrasting with no differences between the two groups of mice without
contrast agent injection in regions of the brain with
amyloid deposition. Our results demonstrated that both approaches were able to identify the differences between AD transgenic mice and wild-type mice, after injected with USPIO-Aβ1-42. The feasibility of using less invasive intravenous femoral
injections for
amyloid plaque detection in AD transgenic mice facilitates using this method for longitudinal studies in the pathogenesis of AD.