Neuroinflammation-targeted magnetic resonance imaging nanoprobes for the early diagnosis of Alzheimer's disease†

Alzheimer's disease (AD) that is an important contributor to dementia, is a chronic and irreversible neurodegenerative disease, with high rates of disability and mortality. Recently, more and more therapeutic methods have been developed to delay the progression of AD, but it remains a great challenge to achieve the early diagnosis of AD. In this work, we developed a magnetic resonance imaging (MRI) nanoprobe (NP@angiopep-2/CD137) based on angiopep-2 peptide and CD137 antibody with a NaGdF₄ nanoparticle as the core and realized neuroinflammation-targeted imaging on APP/PS1 model mice using a clinical 7.0 T MRI scanner. CD137 expression was upregulated in neuroglial cells and cerebral vascular endothelial cells in inflammatory state. In the APP/PS1 mouse model, after administration, the nanoprobe-enhanced images showed specific dot-like signals in the susceptibility-weighted imaging (SWI) sequence. In summary, we designed and synthesized NP@angiopep-2/CD137 nanoprobes using the activation-dependent expression of CD137, which were applied to the pathological assessment of AD based on the hypothesis of AD neuroinflammation, and provided a reliable idea for the early molecular imaging diagnosis of AD.