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Magnetic resonance imaging and circulating molecular testing are potential methods for diagnosing and treating Parkinson's disease (PD). However, their relationships remain insufficiently studied. Using genome-wide association summary statistics, we found in the general population a genetic negative correlation between white matter tract mean diffusivity and PD (-0.17 < Rg < -0.11, p < 0.05), and a positive correlation with intracellular volume fraction (0.12 < Rg < 0.2, p < 0.05). Additionally, 1345 circulating genes causally linked with white matter tract diffusivity were enriched for muscle physiological abnormalities (padj < 0.05). Notable genes, including LRRC37A4P (effect size = 15.7, p = 1.23E-55) and KANSL1-AS1 (effect size = -15.3, p = 1.13E-52), were directly associated with PD. Moreover, 23 genes were found linked with genetically correlated PD-IDP pairs (PPH4 > 0.8), including SH2B1 and TRIM10. Our study bridges the gap between molecular genetics, neuroimaging, and PD pathology, and suggests novel targets for diagnosis and treatment.
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http://dx.doi.org/10.1038/s41531-024-00859-z | DOI Listing |
Neurology
October 2025
Montreal Neurological Institute-Hospital, McGill University, Montreal, Canada.
Background And Objectives: Years before diagnosis of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA), mild prodromal manifestations can be detected. Longitudinal follow-up of people with prodromal synucleinopathy, particularly idiopathic/isolated REM sleep behavior disorder (iRBD), enables in-depth clinical phenotyping of early disease, which could facilitate stratification for clinical trials, provide the definition of appropriate end points, or predict phenoconversion more precisely. The aim of this study was to update and expand on previous studies assessing clinical evolution from iRBD to clinically diagnosed disease, up to 14 years before diagnosis.
View Article and Find Full Text PDFJ Xray Sci Technol
September 2025
Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Qingdao, China.
Parkinson's disease (PD) is a challenging neurodegenerative condition often prone to diagnostic errors, where early and accurate diagnosis is critical for effective clinical management. However, existing diagnostic methods often fail to fully exploit multimodal data or systematically incorporate expert domain knowledge. To address these limitations, we propose MKD-Net, a multimodal and knowledge-driven diagnostic framework that integrates imaging and non-imaging clinical data with structured expert insights to enhance diagnostic performance.
View Article and Find Full Text PDFArch Pharm Res
September 2025
College of Pharmacy, Hanyang University, Ansan, 15588, Republic of Korea.
c-Jun N-terminal kinases (JNKs), a subfamily of mitogen-activated protein kinases (MAPKs), are key mediators of cellular responses to environmental stress, inflammation, and apoptotic signals. The three isoforms-JNK1, JNK2, and JNK3 exhibit both overlapping and isoform-specific functions. While JNK1 and JNK2 are broadly expressed across tissues and regulate immune signaling, cell proliferation, and apoptosis, JNK3 expression is largely restricted to the brain, heart, and testis, where it plays a crucial role in neuronal function and survival.
View Article and Find Full Text PDFClin Auton Res
September 2025
Department of Neurology, University of Utah, Salt Lake City, UT, USA.
J Neurol
September 2025
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background: The "Systematic Screening of Handwriting Difficulties in Parkinson's Disease" (SOS) test is the only tool specifically designed to evaluate handwriting in people with Parkinson's Disease (pwPD). It is language specific.
Objective: To assess the construct validity, intrarater and interrater reliability of the Italian version of the SOS test.