A 9-microRNA Signature in Serum Serves as a Noninvasive Biomarker in Early Diagnosis of Alzheimer’s Disease

Article type: Research Article

Authors: Guo, Rui^a | Fan, Gang^a | Zhang, Jian^a | Wu, Chunxiao^a | Du, Yifeng^b | Ye, Hui^c | Li, Zhang^a | Wang, Lili^a | Zhang, Zhihui^a | Zhang, Lu^a | Zhao, Yueran^{d; *} | Lu, Zhiming^{a; *}

Affiliations: [a] Department of Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P. R. China | [b] Department of Neurology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P. R. China | [c] Department of Quality Management, Blood Center of Shandong Province, Jinan, P. R. China | [d] Department of Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P. R. China

Correspondence: [*] Correspondence to: Zhiming Lu, Department of Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250021, P.R. China. Tel./Fax: +86 53168772466; E-mail: [email protected] and Yueran Zhao, Department of Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250021, P.R. China. Tel.: +86 53168776905; Fax: +86 53187906016; E-mail: [email protected].

Abstract: Alzheimer’s disease (AD) is the most common type of age-related neurodegenerative disorder; nevertheless, nowadays there are no reliable biomarkers or non-invasive techniques available for its early detection. Recent studies have indicated that the circulating level profiles of microRNAs (miRNAs) have the potential to be used as valuable biomarkers for diagnosis, staging, and progress monitoring of various diseases. Here we report a novel 9-miRNA signature (hsa-miR-26a-5p, hsa-miR-181c-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-148b-5p, hsa-miR-106b-3p, hsa-miR-6119-5p, hsa-miR-1246, and hsa-miR-660-5p) that can be utilized as biomarker for detecting AD. We respectively profiled the serum miRNAs from 19 AD patients and 9 healthy control (HC) participants using the Next-Generation Sequencing (NGS). The NGS results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) on a larger cohort of 121 AD and 86 HC cases. All the patients were divided into three groups (mild, moderate, and severe AD) based on the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Our research indicates that abnormal expression of distinct serum miRNAs occurs at different stages of AD. The difference of the area under the receiver operator characteristics curve (AUC) between the AD and the HC is between 70% and 85%. Among the 9 miRNAs, hsa-miR-22-3p has the best sensitivity (81.8%) and specificity (70.9%). The miRNA-panel is more valuable for AD diagnosis. The data suggest that the differentially expressed serum miRNAs could be used as biomarkers to improve the diagnosis of AD, particularly at the early stage, and to classify its clinical stages.

Keywords: Alzheimer’s disease, biomarker, microRNAs, next-generation sequencing, quantitative Real-Time PCR, serum

DOI: 10.3233/JAD-170343

Journal: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1365-1377, 2017