Poison Control Center, Toulouse University Hospital, Toulouse, France.
ToNIC, INSERM UMR1214, Toulouse, France.
J Gerontol A Biol Sci Med Sci. 2024 Mar 1;79(3). doi: 10.1093/gerona/glad208.
The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in the human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from 8 patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and perfluorooctanesulfonate in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared with those with only 1 or neither. Two previous studies have shown that PFAS levels in human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide the first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.
整个人类群体在其一生中都会接触到持久性有机污染物。其中，全氟和多氟烷基物质（PFAS）是广泛用于工业和消费产品的合成化学物质，已知对人类健康有不良影响。由于它们在人体大脑中生物累积，并在实验模型中被证明具有神经毒性，因此它们被认为与神经退行性过程有关。在这项概念验证研究中，我们测量了 8 名因疑似正常压力脑积水住院的患者脑脊液（CSF）中的 18 种 PFAS 水平。然后，我们分析了 PFAS 水平是否与阿尔茨海默病的生物学和临床标志物有关。我们表明，在没有氟化学工业的法国一个地区的所有 CSF 样本中都发现了 PFAS 和全氟辛烷磺酸。此外，我们观察到阿尔茨海默病标志物和认知障碍患者的 CSF 中 PFAS 和全氟辛烷磺酸的水平与仅有 1 种标志物或两者均无的患者有显著差异。此前有两项研究表明，人 CSF 中的 PFAS 水平随年龄增长而增加，并与血脑屏障完整性受损有关。我们的研究结果首次提供了 PFAS 在中枢神经系统中积累与阿尔茨海默病的临床和生物学标志物之间存在关联的证据。
