Molecular design of MRI probes for targeting amyloid-β species: from

The aberrant aggregation of amyloid-β (Aβ) is a central pathological marker of Alzheimer's disease (AD) and shows different neurotoxic properties in various forms, such as monomers, oligomers, fibers and plaques. In recent years, great progress has been achieved in the molecular design and the development of magnetic resonance imaging (MRI) probes targeting Aβ species. They provide powerful tools for the early diagnosis and pathological investigation of AD. Here, we systematically review the molecular design strategies and recent advances in Aβ-targeted MRI probes. First, we introduce the molecular pathological basis of Aβ aggregation and the importance of Aβ as an imaging target. Second, we detail the core components of probe design, including the selection of targeting ligands (e.g., peptide mimetics, small molecules, and antibody fragments), optimization of signal units (e.g., Gd(III), Mn(II), superparamagnetic iron oxide nanoparticles (SPIONs), and ¹⁹F), and the delivery strategies to enhance blood-brain barrier (BBB) penetration. We focus on how the probes achieve the transition from high-affinity binding