机构:[1]Inovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China神经内科首都医科大学宣武医院[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China[6]National Clinical Research Center for Geriatric Disorders, Beijing, China[7]Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ZJ, China
ObjectiveTo give a new insight into the mechanism of ApoE dysregulation and microRNA-1908 in Alzheimer's disease (AD). MethodsPlasma 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 A42 in the culture medium of cell lines. ResultsWe found plasma ApoE level reduced in AD patients (2.28 vs 3.78g/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 3untranslated region. Consistently, microRNA-1908 inhibits the ApoE-mediated A clearance. ConclusionsOur study provides new insight into the mechanism of ApoE dysregulation in AD patients, and microRNA-1908 might be a therapeutic target for AD treatment.
基金:
the Key Project of the National Natural Science Foundation of China (81530036);
the National Key Scientific Instrument and EquipmentDevelopment Project (31627803);
Mission Program of Beijing Municipal Administration of Hospitals (SML20150801);
Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science and Technology Commission (Z161100000216137);
CHINA‐CANADA Joint Initiative on Alzheimer's Disease and Related Disorders(81261120571)
Beijing Municipal Commission of Health and Family Planning (PXM2017_026283_000002);
“Brand Team” Foundation in the First Affiliated Hospital of Wenzhou Medical University.
第一作者机构:[1]Inovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China[6]National Clinical Research Center for Geriatric Disorders, Beijing, China
通讯作者:
通讯机构:[*1]Department of Neurology, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing 100053, China.
推荐引用方式(GB/T 7714):
Z. Wang,W. Qin,C.B. Wei,et al.The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid clearance by targeting ApoE[J].INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY.2018,33(7):980-986.doi:10.1002/gps.4881.
APA:
Z. Wang,W. Qin,C.B. Wei,Y. Tang,L.N. Zhao...&J. Jia.(2018).The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid clearance by targeting ApoE.INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,33,(7)
MLA:
Z. Wang,et al."The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid clearance by targeting ApoE".INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY 33..7(2018):980-986