Inovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China.
Int J Geriatr Psychiatry. 2018 Jul;33(7):980-986. doi: 10.1002/gps.4881. Epub 2018 Apr 10.
To give a new insight into the mechanism of ApoE dysregulation and microRNA-1908 in Alzheimer's disease (AD).
Plasma ApoE levels were measured in 20 AD patients and 20 healthy controls. THP-1 was maintained in RPMI1640 with 10% fetal bovine serum. Quantitative real-time polymerase chain reaction was performed to detect 13-microRNA and ApoE mRNA in cultured cell lines. Enzyme-linked immunosorbent assay was used to measure human ApoE in the plasma or culture medium of cell lines and also used to quantify the human Aβ42 in the culture medium of cell lines.
We found plasma ApoE level reduced in AD patients (2.28 vs 3.78 μg/mL, P < .001), and microRNA-1908 was up-regulated in AD patients and was negatively associated with plasma ApoE (r = -0.32, P = .012). In human macrophage cell line THP-1 and astrocytoma cell line U87, microRNA-1908 could inhibit the mRNA and protein levels of ApoE by targeting its 3'untranslated region. Consistently, microRNA-1908 inhibits the ApoE-mediated Aβ clearance.
Our study provides new insight into the mechanism of ApoE dysregulation in AD patients, and microRNA-1908 might be a therapeutic target for AD treatment.
深入了解载脂蛋白 E 失调和 microRNA-1908 在阿尔茨海默病（AD）中的作用机制。
检测 20 例 AD 患者和 20 例健康对照者的血浆载脂蛋白 E 水平。THP-1 细胞在含 10%胎牛血清的 RPMI1640 培养基中培养。采用实时定量聚合酶链反应检测培养细胞系中的 13 种 microRNA 和载脂蛋白 E mRNA。酶联免疫吸附试验用于检测细胞系血浆或培养上清液中的人载脂蛋白 E，也用于定量检测细胞系培养上清液中的人 Aβ42。
我们发现 AD 患者的血浆载脂蛋白 E 水平降低（2.28 比 3.78μg/ml，P<0.001），且 AD 患者的 microRNA-1908 上调，与血浆载脂蛋白 E 呈负相关（r=-0.32，P=0.012）。在人巨噬细胞系 THP-1 和星形细胞瘤系 U87 中，microRNA-1908 可通过靶向其 3'非翻译区抑制载脂蛋白 E 的 mRNA 和蛋白水平。同样，microRNA-1908 可抑制载脂蛋白 E 介导的 Aβ清除。
本研究为 AD 患者载脂蛋白 E 失调的机制提供了新的见解，microRNA-1908 可能是 AD 治疗的潜在治疗靶点。
