Department of Pharmacology, Sarajevo Medical School, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina.
Department of Cardiology, General Hospital "Prim.Dr. Abdulah Nakas", Sarajevo, Bosnia and Herzegovina.
J Alzheimers Dis. 2020;77(1):375-386. doi: 10.3233/JAD-200358.
Alzheimer's disease is a complex disorder of unclear etiology that develops in the elderly population. It is a debilitating, progressive neurodegeneration for which disease-modifying therapies do not exist. Previous studies have suggested that, for a subset of patients, dysregulation in hemostasis might be one of the molecular mechanisms that ultimately leads to the development of neurodegeneration resulting in cognitive decline that represents the most prominent symptomatic characteristic of Alzheimer's disease.
To examine a relationship between factors that are part of coagulation and anticoagulation pathways with cognitive decline that develops during Alzheimer's disease.
SOMAscan assay was used to measure levels of coagulation/anticoagulation factors V, VII, IX, X, Xa, XI, antithrombin III, protein S, protein C, and activated protein C in plasma samples obtained from three groups of subjects: 1) subjects with stable cognitively healthy function, 2) subjects with stable mild cognitive impairment, and 3) subjects diagnosed with probable Alzheimer's disease.
Our results show that protein levels of coagulation factor XI are significantly increased in patients who are diagnosed with probable Alzheimer's disease compared with cognitively healthy subjects or patients diagnosed with mild cognitive impairment. Furthermore, our results demonstrate that significant predictors of Alzheimer's-type diagnosis are factors IX and XI-an increase in both factors is associated with a reduction in cognitive function.
Our study justifies further investigations of biological pathways involving coagulation/anticoagulation factors in relation to dementia, including dementia resulting from Alzheimer's-type neurodegeneration.
阿尔茨海默病是一种病因不明的复杂疾病，发生于老年人群体。它是一种使人虚弱的、进行性的神经退行性疾病，目前尚无针对这种疾病的疗法。先前的研究表明，对于一部分患者而言，止血功能失调可能是导致神经退行性变的分子机制之一，而神经退行性变最终会导致认知能力下降，这是阿尔茨海默病最突出的症状特征。
探究凝血和抗凝途径相关因子与阿尔茨海默病患者认知能力下降之间的关系。
使用 SOMAscan 检测法测量三组受试者血浆样本中的凝血/抗凝因子 V、VII、IX、X、Xa、XI、抗凝血酶 III、蛋白 S、蛋白 C 和活化蛋白 C 的水平，这三组受试者分别为：1）认知功能稳定的健康受试者；2）认知功能稳定的轻度认知障碍受试者；3）被诊断为可能患有阿尔茨海默病的患者。
我们的研究结果表明，与认知健康的受试者或被诊断为轻度认知障碍的患者相比，被诊断为可能患有阿尔茨海默病的患者的凝血因子 XI 蛋白水平显著升高。此外，我们的研究结果表明，IX 和 XI 因子是阿尔茨海默病样诊断的显著预测因子，这两种因子的增加均与认知功能下降相关。
我们的研究证实，凝血/抗凝因子相关的生物学途径值得进一步研究，以了解其与痴呆症（包括阿尔茨海默病样神经退行性变导致的痴呆症）的关系。
