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University of Minnesota

Nano Lett., Nov 01 2024, | https://doi.org/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

Peter R Christenson ^1,2, Hyeonjeong Jeong ¹, Manci Li ^1,2, Hyerim Ahn ¹, Ann M Schmeichel ³, Pinaki Misra ³, Danni Li ⁴, Rodolfo Savica ³, Phillip A Low ³, Wolfgang Singer ³, Peter A Larsen^2,5, Hye Yoon Park ¹, Sang-Hyun Oh^1,2

¹Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota 55455, United States.

²Minnesota Center for Prion Research and Outreach, University of Minnesota, St. Paul, Minnesota 55108, United States.

³Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, United States.

⁴Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, United States.

⁵Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108, United States.

Corresponding Authors : Peter A. Larsen, Hye Yoon Park, Sang-Hyun Oh

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.

논문정보

형식Research article
게재일2024년 11월 (BRIC 등록일 2024-11-12)
연구진국외 연구진
분야 바이오·의료융합 > 뇌인지과학

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