Blood-Based Nanoparticle-Enhanced Quaking-Induced Conversion (Nano-QuIC): Inhibitor-Resistant Detection of Seeding Activity in Patients Diagnosed with Parkinson's Disease

Peter R Christenson; Hyeonjeong Jeong; Manci Li; Hyerim Ahn; Ann M Schmeichel; Pinaki Misra; Danni Li; Rodolfo Savica; Phillip A Low; Wolfgang Singer; Peter A Larsen; Hye Yoon Park; Sang-Hyun Oh

doi:10.1021/acs.nanolett.4c03768

Blood-Based Nanoparticle-Enhanced Quaking-Induced Conversion (Nano-QuIC): Inhibitor-Resistant Detection of Seeding Activity in Patients Diagnosed with Parkinson's Disease

Nano Lett. 2024 Nov 1. doi: 10.1021/acs.nanolett.4c03768. Online ahead of print.

Authors

Peter R Christenson^{1

2}, Hyeonjeong Jeong¹, Manci Li^{1

2}, Hyerim Ahn¹, Ann M Schmeichel³, Pinaki Misra³, Danni Li⁴, Rodolfo Savica³, Phillip A Low³, Wolfgang Singer³, Peter A Larsen^{2

5}, Hye Yoon Park¹, Sang-Hyun Oh^{1

2}

Affiliations

¹ Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota 55455, United States.
² Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota 55108, United States.
³ Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, United States.
⁴ Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, United States.
⁵ Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108, United States.

PMID: 39485864
DOI: 10.1021/acs.nanolett.4c03768

Abstract

A hallmark of α-synucleinopathies (e.g., Parkinson's disease) is the misfolding and aggregation of α-synuclein in tissues and biological fluids. Protein amplification assays like real-time quaking-induced conversion (RT-QuIC) are sensitive yet currently limited to semi-invasive sample types such as cerebrospinal fluid because more accessible samples, such as blood, contain inhibitors. Here, we show that Nanoparticle-enhanced Quaking-induced Conversion (Nano-QuIC) can double the speed of reactions spiked with misfolded α-synuclein while increasing sensitivity 100-fold in human plasma. Nano-QuIC detected spike concentrations down to 90 pg/mL in lysed whole blood, while reactions without nanoparticles (RT-QuIC) failed to have any detection due to the presence of strong inhibitors. Moreover, Nano-QuIC showed increased seeding activity in plasma samples from Parkinson's patients (n = 4) versus healthy controls (n = 4). This sets the groundwork for the noninvasive diagnostic use of Nano-QuIC, potentially enabling early disease detection and management through blood-based testing.

Keywords: Nanoparticle-enhanced Quaking-induced Conversion (Nano-QuIC); Parkinson’s disease; disease diagnostics; real-time quaking-induced conversion (RT-QuIC); seeded amplification assay (SAA); α-synuclein.