Rosén Christoffer, Mitre Bernardo, Nellgård Bengt, Axelsson Markus, Constantinescu Radu, Andersen Peter Munch, Dalla Keti, Blennow Kaj, Nilsson Gustav, Zetterberg Henrik, Rosén Hans
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Department of Neurology, Institute of Clinical Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Neurol Sci. 2024 Aug 15;463:123112. doi: 10.1016/j.jns.2024.123112. Epub 2024 Jun 25.
Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses. The ALS diagnosis is made by clinical judgement and results from examinations. We aimed to study if the CSF biomarkers neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), YKL-40, soluble amyloid precursor protein (sAPP) α and β, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) were associated with ALS diagnosis and could predict disease progression. Eighty-one patients with suspected ALS were included after referral to the neurological clinic at Sahlgrenska University Hospital. Fifty-nine patients were diagnosed having ALS, while 22 patients were given alternative diagnoses and labeled ALS mimics. Finally, 25 age-matched neurologically intact individuals were used as controls. ALS patients had significantly higher CSF levels of NFL than controls and mimics. Levels of YKL-40 and GFAP were significantly higher in ALS patients compared with controls. No difference was found between study groups when comparing levels of sAPPα, sAPPβ and sTREM2. Further, elevated levels of NFL and YKL-40 were associated with an increased hazard of death and the annual decline in ALSFRS-R. We also found that patients with elevated levels of both NFL and YKL-40 had a particularly poor prognosis. The results demonstrate the usefulness of CSF biomarkers in the diagnosis and prognostication of ALS.
肌萎缩侧索硬化症（ALS）是一种尚无有效治疗方法的神经疾病。在散发性病例中，没有特异性的检测方法能够诊断ALS。疑似病例的常规检查包括神经系统检查、脑和脊柱成像以及由血液和脑脊液（CSF）分析辅助的肌电图检查。ALS的诊断是通过临床判断和各项检查结果做出的。我们旨在研究脑脊液生物标志物神经丝轻链蛋白（NFL）、胶质纤维酸性蛋白（GFAP）、YKL-40、可溶性淀粉样前体蛋白（sAPP）α和β以及髓系细胞表面表达的可溶性触发受体2（sTREM2）是否与ALS诊断相关，以及能否预测疾病进展。81例疑似ALS患者在被转诊至萨尔格伦斯卡大学医院神经科门诊后被纳入研究。59例患者被诊断为患有ALS，而22例患者被给予其他诊断并标记为ALS疑似病例。最后，25名年龄匹配的神经功能正常个体被用作对照。ALS患者脑脊液中NFL水平显著高于对照组和疑似病例组。与对照组相比，ALS患者YKL-40和GFAP水平显著更高。在比较sAPPα、sAPPβ和sTREM2水平时，各研究组之间未发现差异。此外，NFL和YKL-40水平升高与死亡风险增加以及ALS功能评定量表修订版（ALSFRS-R）的年度下降相关。我们还发现，NFL和YKL-40水平均升高的患者预后特别差。结果表明脑脊液生物标志物在ALS的诊断和预后评估中具有重要作用。
