Hudák Anett, Letoha Annamária, Letoha Tamás
Pharmacoidea Ltd., H-6726 Szeged, Hungary.
Department of Internal Medicine, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary.
Int J Mol Sci. 2025 Jul 9;26(14):6587. doi: 10.3390/ijms26146587.
Syndecan-3 (SDC3), a transmembrane heparan sulfate proteoglycan involved in cell signaling and endocytosis, has recently been implicated in the pathogenesis of neurodegenerative disorders. While preclinical studies have demonstrated its role in Alzheimer's disease (AD), its diagnostic relevance in peripheral blood remains unexplored. In this human cohort study, we measured SDC3 expression in peripheral blood mononuclear cells (PBMCs) from 22 clinically diagnosed AD patients and 20 cognitively unimpaired non-AD controls using a custom ELISA. The findings were compared with plasma p-tau217 levels and a panel of systemic laboratory markers. PBMC-expressed SDC3 was significantly elevated in AD patients and moderately correlated with AD status ( = 0.309, = 0.0465) independent of age. Notably, SDC3 levels were inversely correlated with systemic inflammatory markers, including C-reactive protein (CRP; = -0.421, = 0.0055) and D-dimer ( = -0.343, = 0.038), suggesting an AD-associated immune phenotype distinct from acute-phase or vascular inflammation. Conversely, plasma p-tau217 levels did not significantly differ between groups but correlated with markers of tissue injury and inflammation (LDH, GOT, and ferritin), potentially reflecting systemic influences in non-AD controls. A multivariable logistic regression model incorporating SDC3, p-tau217, and age demonstrated high diagnostic accuracy (AUC = 0.85). These findings identify PBMC-expressed SDC3 as a promising blood-based biomarker candidate for AD, warranting further validation in larger, biomarker-confirmed cohorts.
Syndecan-3（SDC3）是一种参与细胞信号传导和内吞作用的跨膜硫酸乙酰肝素蛋白聚糖，最近被认为与神经退行性疾病的发病机制有关。虽然临床前研究已经证明了它在阿尔茨海默病（AD）中的作用，但其在外周血中的诊断相关性仍未得到探索。在这项人类队列研究中，我们使用定制的酶联免疫吸附测定法（ELISA）测量了22例临床诊断为AD的患者和20例认知未受损的非AD对照者外周血单个核细胞（PBMC）中SDC3的表达。将这些结果与血浆p-tau217水平以及一组全身实验室标志物进行了比较。AD患者PBMC中表达的SDC3显著升高，且与AD状态呈中度相关（r = 0.309，P = 0.0465），不受年龄影响。值得注意的是，SDC3水平与全身炎症标志物呈负相关，包括C反应蛋白（CRP；r = -0.421，P = 0.0055）和D-二聚体（r = -0.343，P = 0.038），表明与AD相关的免疫表型不同于急性期或血管炎症。相反，各组之间血浆p-tau217水平没有显著差异，但与组织损伤和炎症标志物（乳酸脱氢酶、谷草转氨酶和铁蛋白）相关，这可能反映了非AD对照者的全身影响。纳入SDC3、p-tau217和年龄的多变量逻辑回归模型显示出较高的诊断准确性（曲线下面积 = 0.85）。这些发现确定PBMC中表达的SDC3是一种有前景的基于血液的AD生物标志物候选物，值得在更大的、经生物标志物证实的队列中进一步验证。
