Alteration of the microRNA network during the progression of Alzheimer's disease

被引:390
|
作者
Lau, Pierre [1 ,2 ,3 ]
Bossers, Koen [4 ]
Janky, Rekin's [5 ]
Salta, Evgenia [1 ,2 ,3 ]
Frigerio, Carlo Sala [1 ,2 ,3 ]
Barbash, Shahar [6 ,7 ]
Rothman, Roy [6 ,7 ]
Sierksma, Annerieke S. R. [1 ,2 ,3 ]
Thathiah, Amantha [1 ,2 ,3 ]
Greenberg, David [6 ,7 ]
Papadopoulou, Aikaterini S. [1 ,2 ,3 ]
Achsel, Tilmann [1 ,2 ,3 ]
Ayoubi, Torik [1 ,2 ,3 ,8 ]
Soreq, Hermona [6 ,7 ]
Verhaagen, Joost [4 ]
Swaab, Dick F. [9 ]
Aerts, Stein [5 ]
De Strooper, Bart [1 ,2 ,3 ]
机构
[1] VIB Ctr Biol Dis, Louvain, Belgium
[2] Katholieke Univ Leuven Hosp, LIND, Ctr Human Genet, Louvain, Belgium
[3] Katholieke Univ Leuven, Louvain, Belgium
[4] Netherlands Inst Neurosci, Neurogenerat Grp, Amsterdam, Netherlands
[5] Catholic Univ Louvain, Ctr Human Genet, Lab Computat Biol, B-3000 Louvain, Belgium
[6] Silberman Inst Life Sci, Dept Biol Chem, Jerusalem, Israel
[7] Edmond & Lily Safra Ctr Brain Sci, Interdisciplinary Ctr Neural Computat, Jerusalem, Israel
[8] St James Sch Med, Bonaire, Dutch Caribbean, Netherlands
[9] Netherlands Inst Neurosci, Neuropsychiat Disorders Grp, Amsterdam, Netherlands
基金
欧洲研究理事会;
关键词
Alzheimer's disease; hippocampus; prefrontal cortex; microRNA; miR-132-3p; MESSENGER-RNA EXPRESSION; TRANSCRIPTION FACTORS; MIRNA; IDENTIFICATION; DYSREGULATION; CONTRIBUTES; SCLEROSIS; DEMENTIA; CLUSTER; NEURONS;
D O I
10.1002/emmm.201201974
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway.
引用
收藏
页码:1613 / 1634
页数:22
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