Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein
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.
Authors
- Harry V. Vinters
- Jiahui Lu (ORCID: https://orcid.org/0000-0002-4941-3098)
- Carolyn J. Hu (ORCID: https://orcid.org/0000-0001-6218-4034)
- Chunni Zhu
- Russell E. Jacobs (ORCID: https://orcid.org/0000-0002-1382-8486)
- Xinyi Cheng (ORCID: https://orcid.org/0000-0003-1654-4363)
- Ke Hou (ORCID: https://orcid.org/0000-0003-3869-2076)
- Christopher Kazu Williams (ORCID: https://orcid.org/0000-0003-3253-7630)
- Shruti Sahay
- Mychica Jones
- M.R. Sawaya (ORCID: https://orcid.org/0000-0003-0874-9043)
- Neil Harris (ORCID: https://orcid.org/0000-0002-5012-2917)
- Hilda Mirbaha
- Marisa Mekkittikul (ORCID: https://orcid.org/0000-0003-1739-9452)
- Xiaohong Zuo
- Naomi S. Sta Maria (ORCID: https://orcid.org/0000-0001-9710-2908)
- Romany Abskharon (ORCID: https://orcid.org/0000-0003-1350-0189)
- Hedieh Shahpasand‐Kroner (ORCID: https://orcid.org/0009-0006-6724-3551)
- Melinda Balbirnie (ORCID: https://orcid.org/0000-0003-3497-392X)
- David Eisenberg (ORCID: https://orcid.org/0000-0003-2432-5419)
- Sally A. Frautschy (ORCID: https://orcid.org/0000-0003-0194-0363)
- Hope Pan (ORCID: https://orcid.org/0000-0001-6509-6224)
- Gregory M. Cole
- Stefano Lepore
- Paul Denver
Institutions
- West Los Angeles College (US)
- University of California, Los Angeles (US)
- Keck Hospital of USC (US)
- UCLA Medical Center (US)
- VA Greater Los Angeles Healthcare System (US)
- Getty Research Institute (US)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1038/s41531-025-00918-z
- Citations
- 1
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- Michael J. Fox Foundation for Parkinson's Research
- California Institute of Technology
- University of Texas Southwestern Medical Center
- National Institutes of Health
- National Institute on Aging
- National Institute of General Medical Sciences
- National Center for Advancing Translational Sciences
- Clinical and Translational Science Institute, University of California, Los Angeles
- California NanoSystems Institute