Amyloid Plaque Imaging with a Targeted MRI Contrast Agent in a Transgenic Mouse Model of Alzheimer’s Disease

Abstract

Purpose: Magnetic resonance imaging (MRI) is a promising technique for detecting amyloid beta (Aβ) deposits in Alzheimer’s disease (AD). Contrast agents can reduce the scanning time and provide specific images to identify various structures. This study aimed to develop an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle coupled with a functional protein as a targeted MRI contrast agent to detect Aβ deposits. Methods: The targeted MRI contrast agent USPIO nanoparticle was coupled with Aβ(16–20) (KLVFF) and HIV-1 trans-activating transcriptor-protein transduction domain (Tat-PTD) to produce the Tat-PTD-USPIO-Aβ(16–20) structure to better penetrate the blood–brain barrier (BBB). In vitro studies were conducted to measure the coupling efficiency, including bicinchoninic acid protein assays, potassium ferrocyanide staining of cardiac microvascular endothelial cells, 1.5T MRI, and toxicity assessments. The contrast agent was injected into five transgenic mice and five age-matched wild-type mice for MRI and histological studies. The targeted agent was diluted, and all mice were scanned with a 7.0 Tesla MRI-scanner. The brain tissues were processed as frozen sections for Thioflavin-S staining to detect Aβ. Results: The coupling efficiency reached 97.75%. The developed MRI contrast agent successfully passed through biological membranes, bound to Aβ deposits, and decreased the MRI signal of tissue in vitro and in vivo. Compared with Aβ(16–20) or Aβ(1–40) alone, there was no significant toxicity of Tat-PTD or Aβ(16–20) when coupled with USPIO nanoparticles. Conclusion: Our novel MRI contrast agent USPIO nanoparticle coupled with functional protein can pass through biological membranes in vitro and visualize Aβ deposits in AD animal models by MRI.