Plasma neurofilament light as a promising biomarker in neuronal intranuclear inclusion disease

• Published in: Journal of neurology Vol. 271; no. 4; pp. 2042 - 2052
• Main Authors: Liu, Minglei, Zhu, Yuru, Yuan, Yanpeng, Wang, Yangyang, Liu, Xiaojing, Li, Lanjun, Gao, Yuan, Yan, Huimin, Liu, Ruoyu, Cheng, Lin, Yuan, Jing, Wang, Qingzhi, Li, Shuo, Liu, Yutao, Wang, Yanlin, Shi, Changhe, Xu, Yuming, Yang, Jing
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2024; Springer Nature B.V
• Subjects: Activities of daily living; Biomarkers; Cognitive ability; Glial fibrillary acidic protein; Medicine; Medicine & Public Health; Neurodegenerative diseases; Neuroimaging; Neurology; Neuronal-glial interactions; Neuroradiology; Neurosciences; Original Communication; Plasma; Protein gene product 9.5; Substantia alba; Tau protein; Ubiquitin carboxy-terminal hydrolase; Disease severity; Neurofilament light; Biomarker; Neuronal intranuclear inclusion disease; Disease progression
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-023-12160-9

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable biomarkers. This study investigates plasma protein levels as potential biomarkers of disease severity and progression in NIID. In this study, we enrolled 30 NIID patients and 36 age- and sex-matched controls, following them for 1–2 years. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and tau were measured using ultrasensitive single molecule array (Simoa) assays. Disease severity was evaluated with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and CNS symptom counts, in addition to neuroimaging data. Our study revealed that NIID patients has significantly higher plasma NfL (median, 35.2 vs. 8.61 pg/mL, p  < 0.001) and GFAP (102 vs. 79.0 pg/mL, p  = 0.010) levels compared to controls, with NfL emerging as a robust diagnostic marker (AUC = 0.956). NfL levels were notably higher in acute-onset NIID (77.5 vs. 28.8 pg/mL, p  = 0.001). NfL correlated strongly with disease severity, including MMSE ( ρ  = − 0.687, p  < 0.001), MoCA ( ρ  = − 0.670, p  < 0.001), ADL ( ρ  = 0.587, p  = 0.001), CNS symptoms ( ρ  = 0.369, p  = 0.045), and white matter hyperintensity volume ( ρ  = 0.620, p  = 0.004). Higher baseline NfL (≥ 35.2 pg/mL) associated with increased ADL scores, CNS symptoms, and white matter hyperintensity at follow-up. UCH-L1 and total tau levels showed no significant differences. Our results suggested the potential of NfL as a promising biomarker of disease severity and progression in NIID.