CREAGEN-Environmental, Genetic and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 287 Via Campi, 41125 Modena, Italy.
Center for Neurosciences and Neurotechnology, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 287 Via Campi, 41125 Modena, Italy.
Int J Mol Sci. 2022 Aug 30;23(17):9865. doi: 10.3390/ijms23179865.
Selenoprotein P, a selenium-transporter protein, has been hypothesized to play a role in the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's dementia (AD). However, data in humans are scarce and largely confined to autoptic samples. In this case-control study, we determined selenoprotein P concentrations in both the cerebrospinal fluid (CSF) and the serum of 50 individuals diagnosed with ALS, 30 with AD, 54 with mild cognitive impairment (MCI) and of 30 controls, using sandwich enzyme-linked immunosorbent assay (ELISA) methods. We found a positive and generally linear association between CSF and serum selenoprotein P concentrations in all groups. CSF selenoprotein P and biomarkers of neurodegeneration were positively associated in AD, while for MCI, we found an inverted-U-shaped relation. CSF selenoprotein P concentrations were higher in AD and MCI than in ALS and controls, while in serum, the highest concentrations were found in MCI and ALS. Logistic and cubic spline regression analyses showed an inverse association between CSF selenoprotein P levels and ALS risk, and a positive association for AD risk, while an inverted-U-shaped relation with MCI risk emerged. Conversely, serum selenoprotein P concentrations were positively associated with risk of all conditions but only in their lower range. Overall, these findings indicate some abnormalities of selenoprotein P concentrations in both the central nervous system and blood associated with ALS and neurocognitive disorders, though in different directions. These alterations may reflect either phenomena of etiologic relevance or disease-induced alterations of nutritional and metabolic status.
硒蛋白 P 是一种硒转运蛋白,据推测它在神经退行性疾病(如肌萎缩侧索硬化症 (ALS) 和阿尔茨海默病 (AD))的发病机制中发挥作用。然而,人类的数据很少,并且主要局限于尸检样本。在这项病例对照研究中,我们使用夹心酶联免疫吸附测定 (ELISA) 方法测定了 50 名 ALS 患者、30 名 AD 患者、54 名轻度认知障碍 (MCI) 患者和 30 名对照者的脑脊液 (CSF) 和血清中的硒蛋白 P 浓度。我们发现所有组中 CSF 和血清硒蛋白 P 浓度之间存在正相关关系,且通常呈线性关系。AD 患者 CSF 中硒蛋白 P 和神经退行性生物标志物呈正相关,而 MCI 患者则呈倒 U 型关系。AD 和 MCI 患者的 CSF 中硒蛋白 P 浓度高于 ALS 和对照组,而血清中 MCI 和 ALS 患者的硒蛋白 P 浓度最高。逻辑回归和三次样条回归分析显示 CSF 硒蛋白 P 水平与 ALS 风险呈负相关,与 AD 风险呈正相关,与 MCI 风险呈倒 U 型关系。相反,血清硒蛋白 P 浓度与所有疾病的风险呈正相关,但仅在其较低范围内。总的来说,这些发现表明与 ALS 和神经认知障碍相关的中枢神经系统和血液中的硒蛋白 P 浓度存在一些异常,尽管方向不同。这些改变可能反映了病因相关现象或疾病引起的营养和代谢状态的改变。