Characteristic Transformation of Blood Transcriptome in Alzheimer's Disease

Article type: Research Article

Authors: Han, Guangchun^{a; b; 1} | Wang, Jiajia^{a; b; 1} | Zeng, Fan^{c; 1} | Feng, Xuemei^a | Yu, Jun^a | Cao, Hong-Yuan^c | Yi, Xu^c | Zhou, Huadong^c | Jin, Lee-Way^d | Duan, Yong^e | Wang, Yan-Jiang^{c; *} | Lei, Hongxing^{a; e; *}

Affiliations: [a] CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China | [b] Graduate University, Chinese Academy of Sciences, Beijing, China | [c] Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China | [d] MIND Institute, School of Medicine, University of California at Davis, Sacramento, CA, USA | [e] UC Davis Genome Center and Department of Biomedical Engineering, Davis, CA, USA

Correspondence: [*] Correspondence to: Hongxing Lei, CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100029, China. Tel./Fax: +86 10 82995396; E-mail: leihx@big.ac.cn; Yan-Jiang Wang, Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. Tel.: +86 23 68757853; Fax: +86 23 68711956; E-mail: yanjiang_wang@tmmu.edu.cn.

Note: [1] These authors contributed equally to this manuscript.

Abstract: Blood transcriptome has emerged as a potential resource for the discovery of biomarkers for Alzheimer's disease (AD). However, the validity of blood transcriptome in the early diagnosis of AD has yet to be extensively tested. In this work, we analyzed published data on AD blood transcriptome and revealed the characteristic perturbation of cellular functional units, including upregulation of environmental responses (immune response, survival/death signaling, and cellular recycling) and down-regulation of core metabolism (energy metabolism and translation/splicing). This characteristic perturbation was unique to AD based on the comparison with blood transcriptome from other neurological disorders and complex diseases. More importantly, similar perturbation was observed in both AD and mild cognitive impairment (MCI) groups. This perturbation pattern was further validated in our independent microarray experiment in a small Chinese cohort. In addition, the potential effect of aging and lifestyle on blood transcriptome was discussed. Based on the analyses, we propose that the transformation of the blood transcriptome in AD is an integrated part of the disease mechanism and has potential to serve as a reliable biomarker for assisting the early diagnosis as well as monitoring purpose. Therefore, more independent studies on blood transcriptome of AD and MCI with larger sample size are warranted.

Keywords: Blood, energy metabolism, immune response, microarray, ribosome

DOI: 10.3233/JAD-121963

Journal: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 373-386, 2013