Delayed Magnetic Resonance Imaging of Alzheimer's Disease by Using Poly(2-(methacryloyloxy)ethyl phosphorylcholine)-Functionalized Nanoprobes

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, commonly affecting the aged, with pathophysiological changes presenting 15 to 20 years before clinical symptoms. Early diagnosis and intervention are crucial in effectively slowing the progression of AD. In the current study, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC)-functionalized NaGdF₄ nanoparticles (NaGdF₄-PMPC) were developed as magnetic resonance imaging (MRI) contrast agents for targeting alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in AD mice. NaGdF₄-PMPC showed excellent biocompatibility, targeting ability, and MRI performance, with the longitudinal molar relaxivity (r₁) and transverse molar relaxivity (r₂) being 1.21-fold and 1.33-fold higher than those of the clinical contrast agent Gd-DTPA, respectively, resulting in higher-sensitive MR angiography. After intravenous injection, 3D dynamic contrast-enhanced (DCE) MR images with high-resolution vasculature of the mouse brain were obtained. In addition, by using NaGdF₄-PMPC, susceptibility-weighted imaging (SWI) signals in AD mouse brains were greatly retained compared to those in healthy mice for 24 h, emphasizing the excellent targeting ability of NaGdF₄-PMPC. Furthermore, the CD31, α7 nAChRs, and Thioflavin S staining were also utilized to investigate the relationship among vascular inflammation, α7 nAChRs, and amyloid-β (Aβ) deposition in AD mice. This work highlights a promising targeted imaging strategy for the timely diagnosis of AD.

Keywords: Alzheimer’s disease; MR angiography; NaGdF4 nanoprobe; dual-modality; vascular inflammation.