Institute of Transfusion Medicine and Immunology, Heidelberg University, Medical Faculty Mannheim, German Red Cross Blood Service of Baden-Württemberg - Hessen gGmbH, Mannheim, Germany.
Geiselgasteig Ambulance Gruenwald, Munich, Germany.
J Alzheimers Dis. 2019;71(3):993-1004. doi: 10.3233/JAD-190574.
Early diagnosis of Alzheimer's disease (AD) is challenging, and easily accessible biomarkers are an unmet need. Blood platelets frequently serve as peripheral model for studying AD pathogenesis and might represent a reasonable biomarker source.
In the present study, we investigated the potential to differentiate AD patients from healthy controls (HC) based on blood count, platelet morphology, and function as well as molecular markers at the time of first clinical diagnosis.
Blood samples from 40 AD patients and 29 age-matched HC were included for determination of 78 parameter by blood counting, platelet morphometry, aggregometry, flow cytometry (CD62P, CD63, activated fibrinogen receptor), protein quantification of nicotinic acetylcholine receptor α7 (nAChRα7) and caveolin-1 (CAV-1), and miRNA quantification (miR-26b, miR-199a, miR-335). Group comparison between patients and controls was performed in univariate and multivariate statistical analyses.
AD patients showed significantly lower aggregation response to ADP and arachidonic acid and significantly decreased CD62P and CD63 surface expression induced by ADP and U46619 compared to HC. Relative nAChRα7 and CAV-1 expression was significantly higher AD platelets than in HC. Multivariate analysis of 63 parameter revealed significant differences between AD patients and healthy controls. The best performing feature model revealed a sensitivity of 96.6%, a specificity of 80.0%, and a positive predictive value of 89.3%. No grouping could be achieved by using single parameter groups.
Significant differences between platelet characteristics from AD patients and HC at the time of first clinical diagnosis were observed. The best performing parameter can be used as a blood-based biomarker for AD diagnosis in a multivariate model in addition to the standardized mental tests.
阿尔茨海默病（AD）的早期诊断具有挑战性，易于获得的生物标志物是未满足的需求。血小板经常作为研究 AD 发病机制的外周模型，可能代表合理的生物标志物来源。
本研究旨在探讨基于首次临床诊断时的血常规、血小板形态和功能以及分子标志物，区分 AD 患者与健康对照（HC）的潜力。
纳入 40 名 AD 患者和 29 名年龄匹配的 HC 的血液样本，通过血细胞计数、血小板形态学、聚集度测定、流式细胞术（CD62P、CD63、活化纤维蛋白原受体）、烟碱型乙酰胆碱受体α7（nAChRα7）和小窝蛋白-1（CAV-1）的蛋白定量以及 miRNA（miR-26b、miR-199a、miR-335）定量来确定 78 个参数。采用单变量和多变量统计分析比较患者和对照组之间的组间差异。
与 HC 相比，AD 患者对 ADP 和花生四烯酸的聚集反应明显降低，ADP 和 U46619 诱导的 CD62P 和 CD63 表面表达明显降低。AD 血小板中的相对 nAChRα7 和 CAV-1 表达明显高于 HC。对 63 个参数的多变量分析显示 AD 患者与 HC 之间存在显著差异。表现最佳的特征模型显示敏感性为 96.6%，特异性为 80.0%，阳性预测值为 89.3%。使用单个参数组无法进行分组。
在首次临床诊断时，AD 患者和 HC 之间的血小板特征存在显著差异。在标准心理测试的基础上，表现最佳的参数可作为 AD 诊断的多变量模型中的一种基于血液的生物标志物。
