Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein

• DOI: 10.1038/s41531-025-00918-z
• Publication Date: 2025-04-23T18:38:15Z
• Authors: Hope Pan; Melinda Balbirnie; Ke Hou; Naomi S. Sta Maria; Shruti Sahay; Paul Denver; Stefano Lepore; Mychica Jones; Xiaohong Zuo; Chunni Zhu; Hilda Mirbaha; Hedieh Shahpasand...; Marisa Mekkittikul; Jiahui Lu; Carolyn J. Hu; Xinyi Cheng; Romany Abskharon; Michael R. Sawaya; Christopher K. Wi...; Harry V. Vinters; Russell E. Jacobs; Neil G. Harris; Gregory M. Cole; Sally A. Frautschy; David S. Eisenberg
• Keywords: Synucleinopathies

Abstract Aggregation of the protein α-synuclein (α-syn) is the histopathological hallmark of neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Currently, patients with synucleinopathies are diagnosed by physical examination and medical history, often at advanced stages of disease. Because synucleinopathies are associated with α-syn aggregates, and α-syn aggregation often precedes onset of symptoms, detecting α-syn aggregates would be a valuable early diagnostic for patients with synucleinopathies. Here, we design a liganded magnetic nanoparticle (LMNP) functionalized with an α-syn-targeting peptide to be used as a magnetic resonance imaging (MRI)-based biomarker for α-syn. Our LMNPs bind to aggregates of α-syn in vitro, cross the blood-brain barrier in mice with mannitol adjuvant, and can be used as an MRI contrast agent to distinguish mice with α-synucleinopathy from age-matched, wild-type control mice in vivo. These results provide evidence for the potential of magnetic nanoparticles that target α-syn for diagnosis of synucleinopathies.