A Korean research team has identified a new blood protein biomarker candidate that could help diagnose Parkinson's disease. Parkinson's is currently diagnosed mainly based on a patient's symptoms and neurological evaluation, but an objective blood-based indicator has not yet been established.
The protein changes found in Korean patients were reproduced in large overseas datasets such as the UK Biobank, leading to assessments that the findings suggest the potential to develop blood-based diagnostic technology for Parkinson's.
The Korea Brain Research Institute (KBRI) dementia research group teams led by researchers Kim Hyeong-jun, Cheon Mu-gyeong, and Kim Do-geun, together with a team led by neurology professor Lee Ho-won at Kyungpook National University Chilgok Hospital, said they published in the latest issue of the international journal "Brain Communications" research results identifying a combination of proteins that change characteristically in the blood of patients with Parkinson's.
Parkinson's disease is a representative neurodegenerative brain disorder in which dopamine neurons in the brain gradually degenerate, leading to tremor, muscle rigidity, and bradykinesia.
It is currently diagnosed based on a patient's symptoms and neurological examination, with dopamine transporter imaging used as an adjunct when the diagnosis is uncertain. However, an objective indicator that can determine disease status using only blood has not yet been established.
The team first compared plasma proteins from 12 patients with Parkinson's and 15 healthy individuals to identify candidate molecules. They then conducted absolute quantification analyses measuring protein concentrations precisely in a separate cohort of 46 patients and 33 healthy controls.
As a result, patients with Parkinson's showed increased concentrations of interleukin-17C (IL-17C) and interleukin-10 (IL-10), and decreased concentrations of urokinase-type plasminogen activator (uPA; PLAU) and neurotrophin-3 (NTF3).
IL-17C and IL-10 are proteins that regulate immune and inflammatory responses. In particular, IL-17C is a cytokine responsible for signaling among immune cells and is known to be involved in chronic inflammation. This study suggests that changes in IL-17C could serve as an indicator reflecting neuroinflammation occurring in Parkinson's.
uPA is involved in blood coagulation and tissue remodeling, and NTF3 is a neurotrophic factor that plays an important role in neuronal survival and maintenance of synaptic function.
The team improved diagnostic performance through a multi-biomarker analysis that combines several proteins. In particular, the diagnostic performance (AUC) of a model using IL-17C together with uPA was 0.780, showing greater discriminative power than using a single protein.
AUC (area under the curve) is an index that evaluates how well a biomarker distinguishes between disease and normal groups. Generally, the closer it is to 1, the higher the discriminatory ability. The team also confirmed results at the AUC 0.778–0.779 level in repeated validations, assessing the model's stability.
A key feature of this study is that it verified whether biomarkers identified in Korean patients are preserved in other populations. The team conducted additional analyses of data from the UK Biobank, a large population-based study in the United Kingdom, and the Global Neurodegeneration Proteomics Consortium (GNPC), which is centered in the United States.
As a result, several proteins, including IL-17C, uPA, and NTF3, showed changes in the same direction in large overseas datasets. The team explained that this suggests the signals are biological features associated with Parkinson's rather than chance findings limited to a specific patient group.
The team also analyzed links with Alzheimer's pathology. The blood biomarker NfL (neurofilament light chain), which reflects axonal injury, increased significantly in patients with Parkinson's, but there were no clear differences in the Alzheimer's-related indicators pTau181 and the amyloid-beta ratio (Aβ42/Aβ40). This suggests that the protein changes identified in this study are more related to Parkinson's-specific pathophysiology than to Alzheimer's.
These findings do not immediately translate into a Parkinson's diagnostic test available in hospitals. The protein combination presented by the researchers is at the candidate biomarker stage that could assist diagnosis, and for real clinical application, large multicenter studies including early patients and those with other parkinsonian syndromes, as well as reference range validation, are required.
Kim Hyeong-jun of the Korea Brain Research Institute said, "This is translational research that combines precise clinical data from domestic hospitals with protein analysis technologies and confirms reproducibility in independent overseas datasets," adding, "We have laid the groundwork for developing blood test technologies that assist future clinical diagnosis."
Reference material
Brain Communications (2026), DOI: https://doi.org/10.1093/braincomms/fcag282