Alpha‐Synuclein Oligomers Driven T1–T2 Switchable Nanoprobes for Early and Accurate Diagnosis of Parkinson's Disease

Abstract The alpha‐synuclein (α‐syn) oligomers hold a central role in the pathology of Parkinson's disease (PD). Achieving accurate detection of α‐syn oligomers in vivo presents a promising avenue for early and accurate diagnosis of PD. Magnetic resonance imaging (MRI), with non‐invasion and exceptional tissue penetration, offers a potent tool for visualizing α‐syn oligomers in vivo. Nonetheless, ensuring diagnostic specificity remains a formidable challenge. Herein, a novel MRI probe (ASOSN) is introduced, which encompasses highly sensitive antiferromagnetic nanoparticles functionalized with single‐chain fragment variable antibodies, endowing it with the capacity for discerning recognition and binding to α‐syn oligomers and triggering a switchable T1–T2 MRI signal. Significantly, ASOSN possesses the unique capability to accurately discriminate α‐syn oligomers from neuroinflammation in vivo. Moreover, ASOSN facilitates the non‐invasive and precise visualizing of endogenous α‐syn oligomers in living systems. This innovative design heralds the development of a non‐invasive visualization strategy for α‐syn oligomers, marking a pivotal advancement for early and accurate diagnosis of PD.