Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for approximately 60–80% of dementia cases worldwide and is characterized by an accumulation of extracellular senile plaques composed of β-amyloid (Aβ) peptide and intracellular neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein. Sporadic or late-onset AD (LOAD) represents 95 % of the AD cases and its etiology does not appear to follow Mendelian laws of inheritance, thus, implicating the role of epigenetic programming and environmental factors. Apolipoprotein allele 4 (ApoE4), the only established genetic risk factor for LOAD, is suggested to accelerate the pathogenesis of AD by increasing tau hyperphosphorylation, inhibiting the clearance of amyloid-β (Aβ), and promoting Aβ aggregation. Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant, with potential neurotoxic effects, that poses a major threat to the ecosystem and human health. By employing in vivo and in vitro models, the present study investigated PFOS as a potential risk factor for LOAD by assessing its impact on amyloidogenesis, tau pathology, and rodent behavior. Our behavioral analysis revealed that developmentally exposed male and female mice exhibited a strong trend of increased rearing and significantly increased distance traveled in the open field test. Biochemically, GSK3β and total ApoE were increased following developmental exposure, in vivo. Furthermore, in vitro, low concentrations of PFOS elevated protein levels of APP, tau, and its site-specific phosphorylation. Differentiated SH-SY5Y cells exposed to a series of PFOS concentrations, also, had elevated protein expression of GSK3β. These data suggest that total ApoE is inducible by environmental exposure to PFOS.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，约占全球痴呆病例的 60-80%，其特征是由 β-淀粉样蛋白 (Aβ) 肽和含有过度磷酸化的细胞内神经原纤维缠结 (NFT) 组成的细胞外老年斑堆积。 τ蛋白。散发性或迟发性 AD (LOAD) 占 AD 病例的 95%，其病因似乎不遵循孟德尔遗传定律，因此暗示了表观遗传编程和环境因素的作用。载脂蛋白等位基因 4 (ApoE4) 是唯一确定的 LOAD 遗传风险因素，建议通过增加 tau 过度磷酸化、抑制淀粉样蛋白-β (Aβ) 的清除和促进 Aβ 聚集来加速 AD 的发病机制。全氟辛烷磺酸（PFOS）是一种持久性有机污染物，具有潜在的神经毒性作用，对生态系统和人类健康构成重大威胁。通过雇用在体内和体外模型中，本研究通过评估 PFOS 对淀粉样蛋白生成、tau 病理学和啮齿动物行为的影响，研究了 PFOS 作为 LOAD 的潜在风险因素。我们的行为分析显示，发育暴露的雄性和雌性小鼠在野外测试中表现出增加饲养和显着增加行进距离的强烈趋势。生化方面，GSK3β 和总 ApoE在体内发育暴露后增加。此外，体外，低浓度的 PFOS 会提高 APP、tau 及其位点特异性磷酸化的蛋白质水平。暴露于一系列全氟辛烷磺酸浓度的分化 SH-SY5Y 细胞也具有升高的 GSK3β 蛋白表达。这些数据表明，环境暴露于 PFOS 可诱导总 ApoE。