Peripheral Blood MicroRNA Expression Profiles in Alzheimer's Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism.
A series of investigations have been performed regarding microRNA (miRNA, miR) of Alzheimer's disease (AD) patients. However, most of these used microarray with neither validation by PCR nor any follow-up on the biological mechanism implicated by findings. Further, there were rarely any analyses linking clinical phenotype of de novo, drug-naive patients to cellular pathogenic mechanism(s) to date. Microarray screening followed by validation via quantitative PCR (Q-PCR) assays and the relationship between miRNAs and phenotypic indices were evaluated. Additionally, the cellular mechanism of miRNAs through effects of β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) was assessed. We identified 2 specific differentially expressed (DE) miRNAs (miR-339 and miR-425) as potential diagnostic biomarkers for AD and revealed that these DE miRNAs could be involved in modulating the pathogenesis of AD via BACE1 protein inhibition. The findings presented here reveal a detailed snapshot of the profile of peripheral blood mononuclear cells (PBMC) miRNA changes in AD patients, association with clinical phenotype, and potential roles in cellular pathogenesis.
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Ru-Jing
RJ
Ren
Research Laboratory of Cell Regulation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yong-Fang
YF
Zhang
Department of Biochemistry and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, 30322, USA.
Eric B
EB
Dammer
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yi
Y
Zhou
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Li-Ling
LL
Wang
Department of Neurology, Shanghai Putuo District People's Hospital, Shanghai, 200060, China.
Xiao-Hong
XH
Liu
Department of Neurology, Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, 200082, China.
Bei-Lei
BL
Feng
Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden.
Guo-Xin
GX
Jiang
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. chen_sd@medmail.com.cn.|Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. chen_sd@medmail.com.cn.
Sheng-Di
SD
Chen
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. wgneuron@hotmail.com.
Gang
G
Wang
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. qicheng8@aliyun.com.|School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China. qicheng8@aliyun.com.
Qi
Q
Cheng
D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D008403:Mass Screening; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D012372:ROC Curve; D015203:Reproducibility of Results
D020413:3' Untranslated Regions; D035683:MicroRNAs; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
Alzheimer’s disease; Expression profiles; MicroRNA; β-site APP cleaving enzyme