Novel Panel of Long Noncoding RNAs as Diagnostic Biomarkers for Amnestic Mild Cognitive Impairment in Peripheral Blood

Article type: Research Article

Authors: Wang, Tao^{a; b; c; 1; *} | Zhang, Wei^{b; c; 1} | Maclin, Joshua M.A.^d | Xu, Hua^{b; c} | Hong, Bo^{b; c} | Yan, Feng^{b; c} | Liu, Yuanyuan^{b; c} | He, Haining^{b; c} | Liang, Huafeng^a | Li, Chunbo^b | Fang, Yiru^e | Xiao, Shifu^{b; c}

Affiliations: [a] Department of Neurology, Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Wuxi, China | [b] Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China | [c] Alzheimer’s Disease and Related Disorders Center, Shanghai Jiao Tong University, Shanghai, China | [d] Biological Sciences Department, Laboratory for Tissue Engineering and Morphogenesis, Rensselaer Polytechnic Institute, Troy, NY, USA | [e] Department of Psychiatry and Affective Disorders Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Correspondence: [*] Correspondence to: Tao Wang, Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Zhixian Road, Wuxi City, Jiangsu Province 214111, China. Tel.: +86 510 68070555; E-mail: [email protected].

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

Abstract: Background:Long noncoding RNAs (lncRNAs) regulate the pathogenesis of Alzheimer’s disease (AD). Objective:To identify lncRNAs in the peripheral blood as potential diagnostic biomarkers for amnestic mild cognitive impairment. Methods:In the discovery group, a microarray was used to screen for significant differences in lncRNA expression between patients with mild cognitive impairment (MCI) caused by AD and normal controls (NCs) (n = 10; MCI, 5; NC, 5). Furthermore, two analytic groups were assessed (analytic group 1: n = 10; amnestic MCI (aMCI), 5; NC, 5; analytic group 2: n = 30; AD, 10; aMCI, 10; NC, 10) and finalized in the validation group (n = 150; AD, 50; aMCI, 50; NC, 50). In the analytic and validation groups, real-time quantitative reverse-transcription polymerase chain reaction was used to identify differentially expressed lncRNAs between the aMCI and NC groups. Results:We identified 67 upregulated and 220 downregulated lncRNAs among the expression profiles. The panel with lncRNAs T324988, NR_024049, ENST00000567919, and ENST00000549762 displayed the highest discrimination ability between patients with aMCI and NCs. The area under the receiver operating characteristic curve of this combined model was 0.941, with a sensitivity of 92.00% and specificity of 84.00%. Conclusions:This study reports on a panel of four lncRNAs as promising biomarkers to diagnose aMCIs.

Keywords: Alzheimer’s disease, biomarkers, classification, cognitive dysfunction, diagnosis, long noncoding, RNA

DOI: 10.3233/JAD-231446

Journal: Journal of Alzheimer's Disease, vol. 99, no. 4, pp. 1385-1396, 2024