Delayed Magnetic\nResonance Imaging of Alzheimer’s\nDisease by Using Poly(2-(methacryloyloxy)ethyl phosphorylcholine)-Functionalized\nNanoprobes

Alzheimer’s disease (AD) is one of the most common\nneurodegenerative\ndiseases, commonly affecting the aged, with pathophysiological changes\npresenting 15 to 20 years before clinical symptoms. Early diagnosis\nand intervention are crucial in effectively slowing the progression\nof AD. In the current study, poly(2-(methacryloyloxy)ethyl phosphorylcholine)\n(PMPC)-functionalized NaGdF<sub>4</sub> nanoparticles (NaGdF<sub>4</sub>–PMPC) were developed as magnetic resonance imaging (MRI)\ncontrast agents for targeting alpha 7 nicotinic acetylcholine receptors\n(α7 nAChRs) in AD mice. NaGdF<sub>4</sub>–PMPC showed\nexcellent biocompatibility, targeting ability, and MRI performance,\nwith the longitudinal molar relaxivity (<i>r</i><sub>1</sub>) and transverse molar relaxivity (<i>r</i><sub>2</sub>) being 1.21-fold and 1.33-fold higher than those of the clinical\ncontrast agent Gd-DTPA, respectively, resulting in higher-sensitive\nMR angiography. After intravenous injection, 3D dynamic contrast-enhanced\n(DCE) MR images with high-resolution vasculature of the mouse brain\nwere obtained. In addition, by using NaGdF<sub>4</sub>–PMPC,\nsusceptibility-weighted imaging (SWI) signals in AD mouse brains were\ngreatly retained compared to those in healthy mice for 24 h, emphasizing\nthe excellent targeting ability of NaGdF<sub>4</sub>–PMPC.\nFurthermore, the CD31, α7 nAChRs, and Thioflavin S staining\nwere also utilized to investigate the relationship among vascular\ninflammation, α7 nAChRs, and amyloid-β (Aβ) deposition\nin AD mice. This work highlights a promising targeted imaging strategy\nfor the timely diagnosis of AD.