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, 57, 170-177

Transcriptome-wide piRNA Profiling in Human Brains of Alzheimer's Disease

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Transcriptome-wide piRNA Profiling in Human Brains of Alzheimer's Disease

Wenying Qiu et al. Neurobiol Aging.

Abstract

Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimer's disease (AD). Prefrontal cortical tissues of 6 AD cases and 6 controls were examined for piRNA expression levels using an Arraystar HG19 piRNA array (containing 23,677 piRNAs) and genotyped for 17 genome-wide significant and replicated risk SNPs. We examined whether piRNAs are expressed differently between AD cases and controls and explored the potential regulatory effects of risk SNPs on piRNA expression levels. We identified a total of 9453 piRNAs in human brains, with 103 nominally (p < 0.05) differentially (>1.5 fold) expressed in AD cases versus controls and most of the 103 piRNAs nominally correlated with genome-wide significant risk SNPs. We conclude that piRNAs are abundant in human brains and may represent risk biomarkers of AD.

Keywords: Alzheimer's disease; Brain; Differential expression; Microarray; Transcriptome; piRNA.

Conflict of interest statement

Conflict of Interest: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Illustration for the pathways underlying piRNA-AD association
[Solid lines: Directly evidenced by our study; Dash lines: Indirectly evidenced by literatures. ➊ piRNA expression is correlated with the risk SNPs (by eQTL analysis); ➋ piRNAs are hypothesized to be most likely to regulate the expression of the nearest protein-coding genes by sequence complementarity; ➌ mRNA expression of the risk genes is correlated to APOE mRNA expression (by correlation analysis); ➍ mRNA/protein of APOE is expressed in brain (by RNA-Seq, RNA microarray and mass spectrometry-based proteomics microarray analyses); ➎ RNAs/proteins expressed in brain are assumed to have potential brain functions; ➏ many brain functions are assumed to be related to the development of AD; ➐ piRNAs are hypothesized to be related to L1 retrotransposons that are involved in brain functions; ➑ piRNAs are hypothesized to use the transposons to regulate gene expression and cellular function; ➒ mRNAs/proteins of the risk protein-coding genes are expressed in brain (by RNA-Seq, RNA microarray and mass spectrometry-based proteomics microarray analyses); ➓ association between APOE and AD is most robust and widely-recognized; ⓫ many genes have been associated with AD in literatures; ⓬ some genes regulated by piRNAs can control brain functions; ⓭ piRNA expression in brain is detected by microarray analysis; ⓮ some piRNAs can target at brain cells that may be implicated in brain functions; ⓯ piRNAs are associated with AD (by differential expression analysis), which is the main goal of the present study; ⓰ associations between SNPs and AD are identified by GWAS
Figure 2
Figure 2. The differential expression between cases and controls
[X-axis: Fold-change; Y-axis: −log10(p); Red points: the differentially expressed piRNAs with 1.5-fold change and p< 0.05]

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