Ruiz-Ortiz Mariano, Lapeña-Motilva José, Giménez de Bejar Verónica, Bartolomé Fernando, Alquézar Carolina, Martínez-Castillo Minerva, Wagner-Reguero Sonia, Del Ser Teodoro, Nogales María Antonia, Álvarez-Sesmero Sonia, Morales Montserrat, García-Cena Cecilia, Benito-León Julián
Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain.
Group of Neurodegenerative Diseases, Hospital Universitario 12 de Octubre Research Institute (imas12), 28041 Madrid, Spain.
Int J Mol Sci. 2025 May 27;26(11):5122. doi: 10.3390/ijms26115122.
Toxic oil syndrome (TOS) is a multisystemic disease that emerged in Spain in 1981 due to the ingestion of aniline-adulterated rapeseed oil fraudulently sold as olive oil. Although neurological sequelae, including cognitive deficits, have been documented in long-term survivors, it remains unclear whether TOS leads to chronic or progressive neurodegeneration. In this case-control study, we measured blood concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 217 (pTau217) in 50 individuals with clinically confirmed TOS and 50 matched healthy controls. Biomarkers were quantified using ultrasensitive immunoassay platforms (Quanterix SIMOA SR-X and Fujirebio Lumipulse G600II). Group differences were evaluated using non-parametric tests, and multiple linear regression was applied to assess associations between biomarkers and clinical variables. While NfL levels were slightly higher in TOS patients ( = 0.025), no significant group differences were observed for pTau217 or GFAP. Age was a consistent predictor of biomarker levels, particularly for GFAP and pTau217, and female sex was independently associated with higher GFAP concentrations. Lower educational attainment was linked to increased NfL levels. Clinical status (TOS vs. control) did not significantly predict biomarker concentrations in any model. These findings suggest no evidence of overt or ongoing neurodegeneration in long-term TOS survivors as detected by current blood biomarkers. However, the possibility of subtle, compartmentalized, or slowly evolving neurotoxic processes cannot be excluded. Future longitudinal studies incorporating serial biomarker assessments, advanced neuroimaging, and oxidative stress markers are warranted to clarify the long-term neurological consequences of TOS and to detect subclinical trajectories of delayed neurotoxicity in this population.
中毒性油综合征（TOS）是一种多系统疾病，1981年在西班牙出现，原因是食用了被苯胺掺杂的菜籽油，该菜籽油被欺诈性地当作橄榄油出售。尽管长期幸存者中已记录到包括认知缺陷在内的神经后遗症，但TOS是否会导致慢性或进行性神经退行性变仍不清楚。在这项病例对照研究中，我们测量了50例临床确诊为TOS的个体和50例匹配的健康对照者血液中的神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）和磷酸化tau 217（pTau217）浓度。使用超灵敏免疫分析平台（Quanterix SIMOA SR-X和富士瑞必欧Lumipulse G600II）对生物标志物进行定量。使用非参数检验评估组间差异，并应用多元线性回归来评估生物标志物与临床变量之间的关联。虽然TOS患者的NfL水平略高（P = 0.025），但pTau217或GFAP未观察到显著的组间差异。年龄是生物标志物水平的一致预测因素，尤其是对于GFAP和pTau217，女性性别与较高的GFAP浓度独立相关。较低的教育程度与NfL水平升高有关。在任何模型中，临床状态（TOS与对照）均未显著预测生物标志物浓度。这些发现表明，根据目前的血液生物标志物检测，长期TOS幸存者中没有明显或正在进行的神经退行性变的证据。然而，不能排除存在细微的、局部的或缓慢发展的神经毒性过程的可能性。未来有必要进行纳入系列生物标志物评估、先进神经影像学和氧化应激标志物的纵向研究，以阐明TOS的长期神经后果，并检测该人群中延迟神经毒性的亚临床轨迹。
