Braissant O, McLin V A, Sessa D, Pierzchala K
Service of Clinical Chemistry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Department of Pediatrics, Gynecology and Obstetrics, Swiss Pediatric Liver Center, University Hospitals Geneva and University of Geneva, Geneva, Switzerland.
Sci Rep. 2025 Oct 30;15(1):37953. doi: 10.1038/s41598-025-21054-x.
Emerging evidence links liver dysfunction to Alzheimer's disease (AD), though few studies have investigated this connection. While cirrhosis is associated with cognitive impairment, its underlying mechanisms remain poorly understood. This study aimed to assess the presence of central nervous system (CNS) markers of Alzheimer's disease in a rat model of chronic liver disease. Standard histochemical techniques were employed, including Congo red staining for amyloid-β (Aβ) and Gallyas silver staining for tau pathology. Immunohistochemistry was used to evaluate changes in aquaporin (Aqp1, Aqp4, Aqp9) expression and astrocytic glial fibrillary acidic protein (GFAP) levels. Furthermore, blood concentrations of neurodegeneration markers, neurofilament light chain (NfL), Aβ, phosphorylated tau (p-tau), total tau (t-tau), GFAP, and myelin oligodendrocyte glycoprotein (MOG), along with bile acids, were quantified and compared between BDL and SHAM control groups to investigate potential systemic correlates of CNS pathology. CNS analysis revealed the presence of intracellular amyloid-β (iAβ) and abnormal tau aggregates (pre-tangle/tangle stages), consistent with early AD pathology. Additionally, alterations in aquaporin water channels and astrocytic GFAP expression were observed. Peripheral blood analysis showed significant changes in neurodegeneration markers (NfL, Aβ, p-tau, t-tau, GFAP, MOG) and bile acid profiles, reinforcing the systemic nature of neuroinflammatory processes in liver disease. Our findings emphasize liver failure as a significant factor in cognitive decline and increased AD risk. The study advocates for incorporating liver function screening into the diagnostic workup of patients with dementia.
越来越多的证据表明肝功能障碍与阿尔茨海默病（AD）有关，不过很少有研究探讨这种联系。虽然肝硬化与认知障碍有关，但其潜在机制仍知之甚少。本研究旨在评估慢性肝病大鼠模型中阿尔茨海默病中枢神经系统（CNS）标志物的存在情况。采用了标准组织化学技术，包括用于淀粉样β蛋白（Aβ）的刚果红染色和用于tau病理的Gallyas银染色。免疫组织化学用于评估水通道蛋白（Aqp1、Aqp4、Aqp9）表达和星形胶质细胞胶质纤维酸性蛋白（GFAP）水平的变化。此外，对胆管结扎（BDL）组和假手术（SHAM）对照组之间神经变性标志物、神经丝轻链（NfL）、Aβ、磷酸化tau（p-tau）、总tau（t-tau）、GFAP和髓鞘少突胶质细胞糖蛋白（MOG）的血浓度以及胆汁酸进行了定量和比较，以研究CNS病理的潜在全身相关性。CNS分析显示存在细胞内淀粉样β蛋白（iAβ）和异常tau聚集体（前缠结/缠结阶段），与早期AD病理一致。此外，还观察到水通道蛋白水通道和星形胶质细胞GFAP表达的改变。外周血分析显示神经变性标志物（NfL、Aβ、p-tau、t-tau、GFAP、MOG）和胆汁酸谱有显著变化，强化了肝病中神经炎症过程的全身性。我们的研究结果强调肝衰竭是认知衰退和AD风险增加的一个重要因素。该研究主张将肝功能筛查纳入痴呆患者的诊断检查中。
