Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
Adv Exp Med Biol. 2019;1118:71-82. doi: 10.1007/978-3-030-05542-4_4.
In the aging world population, Alzheimer's disease accounts for more than 70% of all cases of dementia and is the sixth leading cause of death. The neurodegenerative processes of this disorder can begin 10-20 years before the clinical symptoms develop. Postmortem brain autopsy of Alzheimer's disease cases reveals characteristic hallmarks like extracellular amyloid plaques and intraneuronal neurofibrillary tangles and synaptic and neuronal disintegration with severe brain atrophy. Some studies have reported that platelets contain the amyloid protein precursor and the secretase enzymes required for the amyloidogenic processing of this protein. Thus, platelets can be a good blood cell-based marker to investigate the onset of Alzheimer's disease. Other studies have indicated cellular and molecular alterations in erythrocytes and lymphocytes from Alzheimer's disease subjects, which emphasize the systemic nature of the disorder. In addition, small extracellular vesicles called exosomes appear to be an important factor during the progression of the disease. These vesicles contain disease-associated molecules such as the amyloid protein precursor and tau protein. In this chapter, we will summarize the recent knowledge on the involvement of lymphocytes, erythrocytes, platelets, and exosomes in the development of Alzheimer's disease. The data will be reviewed with a view to applying the above elements as Alzheimer's disease early preclinical and late-stage biomarkers with potential use for clinical diagnosis, prognosis, and monitoring disease progression and treatment responses.
在老龄化的世界人口中，阿尔茨海默病占所有痴呆症病例的 70%以上，是第六大死亡原因。这种疾病的神经退行性过程可以在临床症状出现前 10-20 年开始。对阿尔茨海默病病例的死后大脑尸检显示出特征性的标志物，如细胞外淀粉样斑块和细胞内神经原纤维缠结以及突触和神经元解体，伴有严重的脑萎缩。一些研究报告称，血小板含有淀粉样蛋白前体和该蛋白淀粉样形成加工所需的内切酶。因此，血小板可以作为一种很好的基于血细胞的标志物来研究阿尔茨海默病的发病情况。其他研究表明，阿尔茨海默病患者的红细胞和淋巴细胞存在细胞和分子改变，这强调了该疾病的全身性。此外，称为外泌体的小细胞外囊泡似乎是疾病进展过程中的一个重要因素。这些囊泡包含与疾病相关的分子，如淀粉样蛋白前体和 tau 蛋白。在本章中，我们将总结最近关于淋巴细胞、红细胞、血小板和外泌体参与阿尔茨海默病发展的知识。将审查这些数据，以期将上述元素作为阿尔茨海默病的早期临床前和晚期生物标志物，具有用于临床诊断、预后以及监测疾病进展和治疗反应的潜在用途。
