Periodontal Status and Saliva Metabolic Signature in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Yang, Yi^{a; 1} | Lv, Jiaxi^{a; 1} | Bai, Huimin^a | Ren, Liang^a | Yang, Jing^b | Ding, Yi^a | Liu, Chengcheng^{a; *} | Chen, Xueping^{b; *}

Affiliations: [a] State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China | [b] Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Correspondence: [*] Correspondence to: Chengcheng Liu, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd section of Renmin South Road, Chengdu, Sichuan, China. E-mail: liuchengcheng519@163.com and Xueping Chen, Department of Neurology,West China Hospital, Sichuan University, Wai Nan Guo Xue Xiang 37#, Chengdu, Sichuan, China. E-mail: chenxueping0606@sina.com.

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

Abstract: Background:Characterizing the periodontal status of patients with Alzheimer’s disease (AD), investigating differences in salivary metabolism between patients with and without AD under the same periodontal conditions, and understanding how it is related to oral flora are critical. Objective:We aimed to examine the periodontal condition of patients with AD and to screen salivary metabolic biomarkers from the saliva of individuals with and without AD with matched periodontal conditions. Furthermore, we aimed to explore the possible relationship between salivary metabolic changes and oral flora. Methods:In total, 79 individuals were recruited into the experiment for periodontal analysis. Especially, 30 saliva samples from the AD group and 30 from healthy controls (HCs) with matched periodontal conditions were selected for metabolomic analysis. The random-forest algorithm was used to detect candidate biomarkers. Among these, 19 AD saliva and 19 HC samples were selected to investigate the microbiological factors influencing the alterations in saliva metabolism in patients with AD. Results:The plaque index and bleeding on probing were considerably higher in the AD group. Further, Cis-3-(1-carboxy-ethyl)-3,5-cyclohexadiene-1,2-diol, dodecanoic acid, genipic acid, and N, N-dimethylthanolamine N-oxide were determined as candidate biomarkers, based on the area under the curve (AUC) value (AUC = 0.95). The results of oral-flora sequencing showed that dysbacteriosis may be a reason for the differences in AD saliva metabolism. Conclusion:Dysregulation of the proportion of specific bacterial flora in saliva plays a vital role in metabolic changes in AD. These results will contribute to further improving the AD saliva biomarker system.

Keywords: Alzheimer’s disease, metabolomics, microbiota, periodontitis, saliva

DOI: 10.3233/JAD-230291

Journal: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 603-613, 2023