title: MicroRNA-135a and -200b, potential Biomarkers for Alzheimer׳s disease, regulate β secretase and amyloid precursor protein.
abstract: Amyloid precursor protein (APP) and β-site amyloid precursor protein cleaving enzyme (BACE-1) play important roles in the generation of Alzheimer׳s disease (AD), a progressive neurodegenerative disorder. In the present study, microRNA (miR) microarray was used to analyze the miR expression profiles in the hippocampi from APP/PS1 transgenic and wild type mice. The miRs with significant alteration and putative targets on APP or BACE-1 were retrieved (miR-135a, -200b and -429). The deregulations of these miRs were confirmed in mice and further verified in AD patient samples by qPCR. Primary mouse hippocampal neurons, SH-SY5Y and HEK293 cells were used to study the function of miRs on APP and BACE-1. We found that miR-135a, which was downregulated significantly in hippocampi from APP/PS1 transgenic mice compared with the wild type control, directly interacted with the 3'-UTR of BACE-1 and repressed its expression and activity. On the other hand, miR-200b and -429, which were downregulated significantly in hippocampi from APP/PS1 transgenic mice compared with the wild type control, targeted the 3'-UTR of APP and repressed its expression. Furthermore, Aβ42 could downregulate miR-200b expression which may generate a vicious cycle resulted in accumulating Aβ42. The levels of miR-135a and -200b in the serum of DAT group were significantly lower than that of control groups (P<0.05). The serum miR-200b level of MCI group was higher than that of DAT group (P<0.05) and lower than that of control group (P<0.05). We also found decreased miR-135a and -200b levels in the cerebrospinal fluid of DAT group compared with the control group (P<0.05). In conclusion, these findings showed that miR-135a, -200b and -429 may take part in the progress of AD; miR-200b was of great potential as noninvasive and easily detected blood-based biomarkers of MCI and DAT patients.
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People׳s Republic of China.
authors.forename: Chen-Geng
authors.initials: CG
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People׳s Republic of China.
authors.forename: Jin-Ling
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People׳s Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing, 100191, People׳s Republic of China. Electronic address: lixiangxue@hsc.pku.edu.cn.
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Xue
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People׳s Republic of China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People׳s Republic of China. Electronic address: peichangwang@yahoo.com.cn.
authors.forename: Pei-Chang
authors.initials: PC
authors.lastname: Wang
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D060825:Cognitive Dysfunction / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C544965:MIRN135 microRNA, human; C533896:MIRN200 microRNA, human; C546363:MIRN429 microRNA, human; C582202:MIRN429 microRNA, mouse; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; C543719:Mirn200 microRNA, mouse; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer׳s disease; Amyloid precursor protein; microRNA; β secretase