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

Abstract

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-β plaques in AD. Here we report studies in AβPP/PS1 transgenic mice, which demonstrate the ability of novel anti-AβPP 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-β detection method delivers an efficacious, non-invasive MRI detection method in transgenic mice.

Iron-Based Superparamagnetic Nanoparticle Contrast Agents for MRI of Infection and Inflammation

“…For instance, iron oxide nanoparticles conjugated to vascular cell adhesion molecule 1 (VCAM-1) have been used to enhance MRI of both neuroinflammation and acute cerebral ischemia [26, 27]. Similarly, our group has conjugated SPIONs to antibodies against amyloid in Alzheimer disease plaques to enhance MRI detection of the plaques [28]. We have more recently developed iron-platinum (Fe-Pt) nanoparticles [29] that target ionized calcium binding adaptor molecule 1 (Iba-1) on activated cerebral microglia to directly reveal neuroinflammation.…”

Therapeutic approaches of magnetic nanoparticles for the central nervous system

“…Similarly, in another in vivo study, Sillerud et al reported the targeting efficacy of anti-Ab protein precursor (PP)-conjugated MNPs. These antibody-conjugated MNPs were able to penetrate the BBB and the detectability of the plaques by MRI was higher in AD transgenic mice than control mice [52]. With this approach early diagnosis of the plaques can be done along with direct measurement of efficacy of the antiamyloid therapies.…”

Amyloid-like fibrils labeled with magnetic nanoparticles

“…The authors could use these nanoparticles to image amyloid plaques by means of μ MRI. Moreover, Sillerud and co-workers could show that conjugation of an anti-amyloid β antibody to iron oxide nanoparticles enabled binding of nanoparticles and contrast enhanced imaging of Alzheimer ' s amyloid plaques (49) .…”