Pharmacoidea Ltd., H-6726 Szeged, Hungary.
Albert Szent-Györgyi Clinical Center, Department of Medicine, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary.
Int J Mol Sci. 2022 Mar 21;23(6):3407. doi: 10.3390/ijms23063407.
Early diagnosis of Alzheimer's disease (AD) is of paramount importance in preserving the patient's mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous system (CNS) degeneration in the periphery. Members of the syndecan family of transmembrane proteoglycans are emerging new targets in inflammatory and neurodegenerative disorders. Reviewing the growing scientific evidence on the involvement of syndecans in the pathomechanism of AD, we analyzed the expression of the neuronal syndecan, syndecan-3 (SDC3), in experimental models of neurodegeneration. Initial in vitro studies showed that prolonged treatment of tumor necrosis factor-alpha (TNF-α) increases SDC3 expression in model neuronal and brain microvascular endothelial cell lines. In vivo studies revealed elevated concentrations of TNF-α in the blood and brain of APPSWE-Tau transgenic mice, along with increased SDC3 concentration in the brain and the liver. Primary brain endothelial cells and peripheral blood monocytes isolated from APPSWE-Tau mice exhibited increased SDC3 expression than wild-type controls. SDC3 expression of blood-derived monocytes showed a positive correlation with amyloid plaque load in the brain, demonstrating that SDC3 on monocytes is a good indicator of amyloid pathology in the brain. Given the well-established role of blood tests, the SDC3 expression of monocytes could serve as a novel biomarker for early AD detection.
早期诊断阿尔茨海默病（AD）对于在相当可管理的条件下延长患者的身心健康非常重要。可靠的 AD 检测需要新的生物标志物来指示中枢神经系统（CNS）在周围的退化。细胞表面蛋白聚糖的 syndecan 家族成员是炎症和神经退行性疾病的新兴新靶点。在回顾 syndecan 参与 AD 发病机制的不断增加的科学证据的基础上，我们分析了神经元 syndecan-3（SDC3）在神经退行性变实验模型中的表达。最初的体外研究表明，肿瘤坏死因子-α（TNF-α）的长期治疗会增加模型神经元和脑微血管内皮细胞系中 SDC3 的表达。体内研究显示，APPSWE-Tau 转基因小鼠的血液和大脑中 TNF-α 浓度升高，大脑和肝脏中 SDC3 浓度升高。从 APPSWE-Tau 小鼠中分离出的原代脑内皮细胞和外周血单核细胞表现出比野生型对照更高的 SDC3 表达。血液衍生单核细胞的 SDC3 表达与大脑中的淀粉样斑块负荷呈正相关，表明单核细胞上的 SDC3 是大脑中淀粉样蛋白病理学的良好指标。鉴于血液检测的既定作用，单核细胞的 SDC3 表达可以作为早期 AD 检测的新型生物标志物。
