Brain Gray Matter Volume Mediated the Correlation Between Plasma P-Tau and Cognitive Function of Early Alzheimer’s Disease in China: A Cross-Sectional Observational Study

Article type: Research Article

Authors: Wan, Ke^{a; 1} | Yin, Wenwen^{a; 1} | Tang, Yating^a | Zhu, Wenhao^a | Wang, Zhiqiang^{b; c} | Zhou, Xia^a | Zhang, Wei^a | Zhang, Cun^d | Yu, Xianfeng^e | Zhao, Wenming^d | Li, Chenchen^a | Zhu, Xiaoqun^a | Sun, Zhongwu^{a; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China | [b] Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China | [c] Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, Tasmania, Australia | [d] Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China | [e] Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China

Correspondence: [*] Correspondence to: Zhongwu Sun, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province 230022, China. Tel.: +86 0551 62922328; E-mail: sunzhwu@126.com.

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

Abstract: Background:The primary manifestations of Alzheimer’s disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear. Objective:To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition. Methods:In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants’ brain GMV. Partial correlation and mediation analyses were conducted in AD group. Results:Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified. Conclusion:The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD.

Keywords: Alzheimer’s disease, cognitive function, gray matter volume, plasma biomarkers, phosphorylated tau

DOI: 10.3233/JAD-221100

Journal: Journal of Alzheimer's Disease, vol. 92, no. 1, pp. 81-93, 2023