Eratne Dhamidhu, Lewis Courtney, Kelso Wendy, Loi Samantha, Chiu Wei-Hsuan Michelle, Blennow Kaj, Zetterberg Henrik, Santillo Alexander F, Velakoulis Dennis, Walterfang Mark
Neuropsychiatry Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
Acta Neuropsychiatr. 2024 Mar 27;37:e20. doi: 10.1017/neu.2024.14.
Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls.
Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges.
Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1 vs. 7.4 pg/ml, < 0.001), and reference ranges (all >98 percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6 vs. 75.1 pg/ml).
The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
尼曼-匹克C型（NPC）病是一种遗传性神经退行性溶酶体贮积症，常伴有精神症状，且诊断和治疗往往延迟。本研究调查了与健康对照相比，NPC患者血浆神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）的生物标志物水平及诊断效用。
从专科评估和管理服务机构招募NPC患者。有来自年龄和性别匹配的健康对照组的数据。使用Quanterix Simoa HD-X分析仪测量NfL和GFAP，并使用广义线性模型对各组进行比较。将NfL水平与最近制定的NfL参考范围进行比较，并得出百分位数。
与25名对照组相比，11名NPC患者的血浆NfL显著升高（平均17.1对7.4 pg/ml，<0.001），且均高于参考范围（均>98百分位数）。NfL能高精度地区分NPC患者与对照组。NPC患者的GFAP水平未升高（66.6对75.1 pg/ml）。
该研究为血浆NfL在NPC诊断中的潜在效用增添了重要证据，将NfL作为区分神经退行性疾病和原发性精神疾病的诊断工具的文献进行了扩展，并支持NPC的病理学主要涉及神经元，尤其是轴突的退化。
